Archive for December, 2009
Families of Spinal Muscular Atrophy Funded Program Shows Quinazoline Compounds Give Survival Benefit in a Severe Mouse Model of SMA.
Last Updated on Monday, 28 December 2009 12:06 Written by Editor Monday, 28 December 2009 12:06
This publication, showing data from the testing of Quinazoline derivatives in a Spinal Muscular Atrophy mouse model, has been published in Human Molecular Genetics by lead author Dr. Matthew Butchbach from the laboratory of Dr. Arthur Burghes at the Ohio State University.
The generation of the Quinazoline compounds as a therapeutic drug candidate for Spinal Muscular Atrophy was fully funded by Families of SMA.
The paper explores whether the Quinazoline compounds, which increase the expression of SMN2, are useful as potential therapeutics for SMA. Ultrahigh-throughput screening identified substituted Quinazolines as potent SMN2 inducers. The drug-like properties of the initial screening hits were optimized through directed medicinal chemistry. This resulted in series of C5-Quinazoline derivatives.
Oral administration of three of these compounds (D152344, D153249 and D156844) to neonatal mice resulted in a dose-dependent increase in Smn promoter activity in the central nervous system.  The authors then examined the effect of these compounds on the progression of disease in SMNDelta7 SMA mice. Oral administration of D156844 significantly increased the mean lifespan of SMNDelta7 SMA mice by approximately 21-30% when given prior to motor neuron loss. Overall the authors summarize that the quinazoline derivative D156844 increases SMN expression in neonatal mouse neural tissues, delays motor neuron loss at PND11, and ameliorates the motor phenotype of SMNDelta7 SMA mice.
“This is the first compound series to go from hit-to-preclinical candidate that shows favorable pharmacology in the nervous system and shows benefit to severe SMA mice. This study shows that promising therapies for SMA can be developedâ€, said Matthew Butchbach, Ph.D., who is lead author on this publication.
“Families of SMA is pleased that the first test of this class of compounds in SMA mice shows potential therapeutic benefit. The clinical lead in this series called Quinazoline495, which is a more optimized compound than those tested here, has also been assessed in this animal model with similar results, as well as tested in a slightly less severe mouse model of SMA, in which it showed marked enhancement of survival”, says Jill Jarecki, Ph.D., FSMA research director.
The lead compound Quinazoline495 recently received orphan drug designation from the FDA for the treatment of spinal muscular atrophy. Please click here to read more.
Families of SMA recently licensed this series of compounds to Repligen Corporation for development as a drug treatment for Spinal Muscular Atrophy.
The full reference:
Butchbach ME, Singh J, Thornorsteinsdóttir M, Saieva L, Slominski E, Thurmond J, Andrésson T, Zhang J, Edwards JD, Simard LR, Pellizzoni L, Jarecki J, Burghes AH, Gurney ME. Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy. (2009). Human Molecular Genetics, Epub ahead of print.
Source: fsma.org
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Enzyme binds both sides of the mirror
Last Updated on Monday, 28 December 2009 11:30 Written by Editor Monday, 28 December 2009 11:30
European chemists have discovered that both mirror-image forms of a particular compound can bind at the same time in the same site of an enzyme, a phenomenon that has never been seen before. The finding has significance for drug discovery screening and studies of how small molecules interact with proteins.
Rolf Breinbauer from Graz University of Technology, Austria, and Wulf Blankenfeldt from the Max Planck Institute of Molecular Physiology in Dortmund, Germany, were studying a metabolic enzyme from a species of the bacterium Burkholderia cepacia, using racemic mixtures of chiral probe molecules to find ones that bound in the enzyme’s active site. In most cases only one form of a chiral (or ‘handed’) molecule would bind at once, but they found that in one instance both enantiomeric forms occupied the binding site at the same time.
‘If you read the textbooks about enantiomers,’ says Breinbauer, ‘there’s a simplified notion that one enantiomer is good and the other is either bad or just idle.’ He explains that for most proteins (apart from certain enzymes that have evolved to cope with wide ranges of substrate molecules) either only one enantiomer will bind, or both can bind individually - with the assumption that one form will be significantly more active than the other. ‘Our findings show that the world is more complicated,’ he adds.
While each individual enantiomer can bind to the enzyme seperately, Breinbauer notes that the arrangement of the molecules within the binding site is quite different when both bind together. This could lead to cooperative effects, producing either an enhanced or diminished response relative to the individual enantiomers.
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The three ways enantiomers can bind in enzymes: only one enantiomer binds (top); each binds individually (middle); both bind together (bottom)
© Angewandte Chemie
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He adds that this could have relevance in drug discovery screening, where mixtures of both enantiomers of chiral compounds are routinely screened together to find initial hits. ‘People need to consider more options when interpreting binding data from racemic mixtures.’
Dafydd Owen of Pfizer Research Chemistry in Sandwich, UK, agrees that the finding is an important reminder that chemists need to be open-minded about interpreting screening data. It also highlights the inherent trade-offs made when screening mixtures - particularly in high-throughput screens when mixtures of several compounds are tested at once.
Owen sees most interest in the discovery in the area of fragment-based drug discovery, where small ‘fragment’ molecules found to bind to a drug target are linked together to make potential drug molecules. ‘As a medicinal chemist,’ he adds, ‘my immediate thought was to join the two structures together to incorporate the best of each and make a hybrid.’ He points out, however, that from a fragment point of view it is almost irrelevant to the enzyme that the two molecules happen to be mirror images of each other, ‘despite their apparent similarity, nature views enantiomers as very different molecules’.
Phillip Broadwith
Source: rsc.org
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UT professor receives grant for new process
Last Updated on Wednesday, 16 December 2009 10:59 Written by Editor Wednesday, 16 December 2009 10:59
Using a pair of tweezers, a UT graduate student carefully lifted a nylon mesh square about the size of a thumbnail out of a small flask in his team’s lab.
The nylon had been soaking in a clear, watery solution containing a chemical compound — the “capture agent†— that it would bind with during a process tweaked by the student and his team.
Jennifer Brodbelt, a chemistry and biochemistry professor, received a $734,068 grant from the National Institutes of Health Oct. 1 to further develop the process — Desorption Electrospray Ionization (TM-DESI) — and perfect the nylon squares which isolate desired compounds from solutions.
Brodbelt, UT graduate students and two professors from Southwestern University in Georgetown were given a two-year deadline to gather blood from people of varying ages and levels of health, and to develop a more efficient method of analyzing the samples.
Results will be used to spot trends in the frequency of certain biological compounds, including amino acids.
A mass spectrometer, the machine Brodbelt’s team uses, can identify specific compounds in a mixture like blood. The tricky part was getting the sample to spray into the machine.
Joe Chipuk, a graduate student currently working on the project, was struck by the idea of having samples sprayed directly through a sifting material into the spectrometer.
Chipuk ran home and began collecting mesh materials to spray water through. He cut up his screen door, his wife’s tea strainer and the aerator from his kitchen faucet.
He went outside, used a hose to spray water through the mesh materials and observed the water’s exit path.
He then drafted a plan to create a mesh material soaked in a chemical that allows certain compounds to travel through but traps enough as to not let every metabolite escape.
After the unwanted materials are sorted out, the desired compounds attached to the mesh are released and analyzed by the spectrometer.
Before Chipuk’s square, the desorption process played out very much like a complicated billiards shot. The spray came down at an angle, hit the slide holding the blood sample and ricocheted off carrying the compounds through the spectrometer.
The new technique allows the compounds to be sorted and analyzed at a much faster pace than before. Chipuk said they can now analyze 50 samples in approximately eight minutes, whereas before, analyzing 50 samples would have taken more than 24 hours.
The team is focusing on improving the reliability and consistency of the mesh squares, Brodbelt said.
“The hope is that this could be a way to diagnose patterns of disease or determine a prognosis based on the pattern of metabolites,†Brodbelt said. “The sooner you have an idea that you might have cancer, or that you are on track to develop cancer, you could have screening done earlier and more frequently.â€
Source: dailytexanonline.com
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Computational Method Points To New Uses, Unexpected Side Effects Of Already Existing Drugs
Last Updated on Tuesday, 15 December 2009 04:19 Written by Editor Tuesday, 15 December 2009 04:19
Scientists at the University of North Carolina at Chapel Hill School of Medicine and the University of California, San Francisco have developed and experimentally tested a technique to predict new target diseases for existing drugs.
The researchers developed a computational method that compares how similar the structures of all known drugs are to the naturally occurring binding partners — known as ligands — of disease targets within the cell. In a study published this week in Nature, the scientists showed that the method predicts potential new uses as well as unexpected side effects of approved drugs.”This approach uncovered interactions between drugs and targets that we never could have predicted simply by looking at the chemical structures,” said senior study author Bryan Roth, M.D., Ph.D., professor of pharmacology and director of the National Institute of Mental Health Psychoactive Drug Screening Program at UNC. “We may now have a way to predict what side effects are likely to occur from treatment before we even put a drug into clinical testing.” Roth is also a member of the UNC Lineberger Comprehensive Cancer Center.
Many of the most successful drugs on the market today are being prescribed for ailments that are quite different from the ones they were originally designed to treat. Viagra, for instance, was once intended for coronary heart disease but now is used to combat erectile dysfunction. The discovery of surprising uses of developed drugs can sometimes be the result of serendipity, as unforeseen side effects emerge from clinical trials. In the past, researchers have tried to predict drug interactions by looking for chemical similarities among the possible targets of pharmaceutical compounds.
However, some drug targets which look very similar to one another bind very different ligands, and some targets that don’t have any obvious similarity bind similar ligands, says Brian Shoichet, Ph.D., co-senior study author and professor of pharmaceutical chemistry at the University of California at San Francisco. “So if instead we were to organize targets by the ligands they recognize, it could reveal different patterns than traditional approaches, and illuminate new opportunities for drugs to bind to unexpected targets.”
A team of researchers led by Roth and Shoichet did just that, comparing the structures of 3,365 FDA-approved and investigational drugs against the structures of hundreds of targets, defining each target by its ligands. They then honed in on thirty of the strongest predictions, validating the actual physical interactions between the drugs and targets in wet laboratory experiments.
In one of their follow-up experiments, the scientists investigated the molecular targets of the hallucinogenic substance dimethyltrytamine (DMT), which had previously been postulated to act through a site known as the sigma-1 receptor. Using the computational approach, Roth and colleagues found that DMT had a high affinity for serotonin receptors, including the binding site for LSD, another hallucinogen.
They also showed that the substance is hallucinogenic in normal mouse models but not in ones lacking the serotonin receptor. Roth says the power of their approach is it can be used to uncover the real targets of pharmaceutical compounds quickly and efficiently, and will probably lead to a greater understanding of the many molecular targets of each drug.
“Drugs are not as selective as we once thought,” said Roth, who is also a professor in the School of Pharmacy’s medicinal chemistry and natural products division. “It turns out that the most non-selective drugs are frequently the most effective for complex diseases. Rather than ‘magic bullets,’ we need to come up with ‘magic shotguns’ that hit more than one molecular target at a time. We could use this computational approach to identify the drugs that hit the right targets and miss the wrong ones.”
Study co-authors from UNC include Vincent Setola, research associate professor; Atheir Abbas, former graduate student; Sandra J. Hufeisen, senior research assistant; Niels H. Jensen, research associate; Michael B. Kuijer, research technician; Roberto C. Matos, research technician; Thuy B. Tran, research technician; Ryan Whaley, research technician; and Richard A. Glennon. The paper’s first author is Dr. Michael Keiser, from the UCSF side of the collaboration. Also from UCSF were Drs. John Irwin, Christian Laggner and Jerome Hert, and PharmDs Kelan Thomas and Douglas Edwards.
Funding for the studies at UNC and at UCSF came from the National Institutes of Health.
ScienceDaily (Nov. 7, 2009)
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Professor Receives Grant to Develop More Rapid Technology For Screening Blood Samples
Last Updated on Tuesday, 15 December 2009 03:29 Written by Editor Tuesday, 15 December 2009 03:29
AUSTIN, Texas — Dr. Jennifer Brodbelt, professor of chemistry and biochemistry at The University of Texas at Austin, has received a $734,068 grant from the National Institutes of Health (NIH) to develop a new method for rapidly screening blood samples for biomarkers.
Biomarkers are small molecules that indicate the presence of a particular physiological condition, typically a disease. The new method, if successful, could prove useful not just for identifying markers of specific diseases such as cancer or heart disease, but for discovering broader metabolic patterns correlated with conditions such as aging or obesity.
“There are technologies right now that are very effective at separating and analyzing the different compounds in a blood sample, but they tend to be relatively slow,” says Brodbelt, the principal investigator of the grant. “It makes it very hard to do analyses of lots of samples. What we’re developing is a chip-based method, where entire classes of compounds are captured on the chips and then all the compounds are released and analyzed by mass spectrometry in just a few seconds.”
Although the technology, if successful, should be useful in searching for biomarkers in all sorts of conditions, Brodbelt and her collaborators from Southwestern University in Georgetown, Texas, Drs. Lynn and Frank Guziec, are focusing on patterns that correlate with aging.
“We’re trying to develop maps that can correlate the progression of aging with metabolites that might be circulating in your blood,” says Brodbelt. “These could be small molecules that increase in quantity as you age, or actually change in composition as one ages.”
The new method, says Brodbelt, involves three basic stages.
The first stage is the coating of different regions of a mesh chip with a variety of “capture agents,” which chemically bind to specific compounds in a blood sample. A burst from an ultraviolet light then severs the chemical bonds between the chip and the captured substances. Then an electrospray, which is similar to a solvent aerosol spray, shoots through the mesh chip and transfers the different compounds into the mass spectrometer for analysis.
By analyzing the mass spectrometric data, says Brodbelt, scientists should be able to measure the presence and quantity of different compounds, and to do so on a scale, and with a speed, that wasn’t possible before.
“The payoff could be big,” she says. “It’s a different strategy than what might be pursued by molecular biologists or biochemists. They’ll often focus on studying one or two proteins at a time, and develop a really deep understanding of those proteins. We’re looking for the more generalized profile, and we may notice some patterns that weren’t apparent to them.
“There are so many other areas where you’d want to do profiling. It might involve looking for pesticides as part of an environmental study, or doing protein-related work or drug profiling work. If this approach is successful, I imagine other groups will try to develop these chips as well.”
Brodbelt’s grant, which is being funded as part of the American Recovery and Reinvestment Act (ARRA) government stimulus package, is a “Challenge Grant,” meant to encourage high-risk, high-reward research projects that may produce results quickly.
This is the second NIH grant in two years that Brodbelt and the Guziecs have received. In 2008, the collaborating groups received a four-year, $1,113,615 grant to evaluate an innovative technique that could assess the anti-cancer activity of new compounds.
For more information, contact: Jennifer Brodbelt, Department of Chemistry and Biochemistry, 512-471-0028.
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Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro
Last Updated on Tuesday, 15 December 2009 03:27 Written by Editor Tuesday, 15 December 2009 03:27
Using a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (>8,000 compounds) directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 microM compound in triplicate with a minimum efficacy of 90% required for lead selection.
Lead compounds were then further characterised to determine the median efficacy (IC50), cytotoxicity (CC50) and the in vitro therapeutic index in live virus and pseudotype assay formats.
Results: While a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound.
Conclusions: All three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies.
Author: Mohamad AljofanMichael SgangaMichael LoChristine RootesMatteo PorottoAdam MeyerSimon SaubernAnne MosconaBruce Mungall
Credits/Source: Virology Journal 2009, 6:187
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Tapeworm Drug May Hold Promise For Colon Cancer, Future Research
Last Updated on Tuesday, 15 December 2009 03:22 Written by Editor Tuesday, 15 December 2009 03:22
The findings about this compound, published in the Nov. 3 issue of Biochemistry journal, might prove valuable to patients and clinicians, who may benefit if there is a demonstrated boost to chemotherapy. Researchers also can use the compound to manipulate the receptor to learn more about a common cell replenishing pathway, called the Wnt pathway, which requires the receptor for normal activities and can go wrong in cancer cases.
The researchers had a choice: to screen libraries of several hundred thousand biochemical compounds or to use a library of about 1,200 FDA approved or biologically active compounds.
“We decided to take the less expensive route of screening FDA approved drugs, and fortunately, we found 26 compounds that seemed to meet our goal, but only one that truly worked with the Frizzled receptor,â€said Wei Chen, Ph.D., Assistant Professor of the Department of Medicine at Duke. “The goal was to drive the Frizzled 1 receptor from the outer membrane to the inside of the cell,†which effectively inactivated the receptor.
The effective compound, niclosamide, is currently approved for use against tapeworm infection. But some colon cancer patients, for example, have a Wnt pathway that is overactivated and may benefit from the “quieting†effects of niclosamide, which blocks the receptor in the Wnt pathway.
“The paper provides a rationale for clinicians to investigate using niclosamide for a new purpose,†Dr. Chen said. “Based on our findings, one oncologist at Duke is writing protocols for a phase 1 (safety) clinical trial to treat colon cancer patients with the intention of bringing our laboratory findings to the patient’s bedside.â€
Chen says he is proud of the work, which is “truly translational science.â€
“I am a basic scientist working with cell receptors, we have a medicinal chemist in our laboratory and one of our collaborators is Dr. H. Kim Lyerly, a professor of surgery, who is a researcher in gene- and immune-based therapies for cancer, as well as director of the Duke Comprehensive Cancer Center,†said Chen. “This type of diverse collaboration lets me shepherd a finding more rapidly from the laboratory to the clinic.â€
Provided by Duke University Medical Center
physorg.com
Posted under Cancer Research, Discoveries, Innovations and Patents, Drug Development, Drug-Like Compounds, Oncology Research, Press Releases | Comments Off
Slow procedure
Last Updated on Monday, 14 December 2009 05:29 Written by Editor Monday, 14 December 2009 05:29
Slow procedure
It takes 15 years on average for a drug discovery to make it to a patient’s medicine cabinet. Throughout the process, the U.S. Food and Drug Administration requires drug companies to submit applications to proceed to the next step.
1 Drug discovery and preclinical research (three to six years) – Researchers search for candidate drugs by screening chemical compounds that contain thousands or millions of potential medicines. They test the candidates against the disease target.
Once a compound has shown some activity against the drug target, it undergoes extensive testing in the lab – both in test tubes and animals. Years of preclinical testing must establish that the candidate medicine is likely to be safe and effective in humans before clinical testing can begin.
2 Clinical trials (six to seven years) – When a company is ready to begin clinical trials, it submits an Investigational New Drug Application to the FDA showing the data it has gathered in preclinical tests, as well as a clinical studies plan or protocol. Testing occurs in three phases:
Phase 1 – A small group of healthy people is tested to see how the chemical compound affects the body.
Phase 2 – The drug is tested in patients who have the disease in question.
Phase 3 – The drug is tested in hundreds or thousands of patients to find any rare or adverse side effects.
3 FDA review and manufacturing (two years) – Upon successful completion of clinical trials, the company submits a New Drug Application to the FDA.
Teams of engineers, biologists, chemists and physicists work to develop ways to produce the medicine on a large scale.
SOURCE: Pharmaceutical Research and Manufacturers of America
Source: Dallasnews.com
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Leishmaniasis: New Strategy To Find Drugs To Treat Neglected Parasitic Infection
Last Updated on Monday, 14 December 2009 05:25 Written by Editor Monday, 14 December 2009 05:25
Using an unconventional approach that they designed, University of Pittsburgh drug discoverers and their collaborators at Walter Reed Army Institute of Research have identified compounds that hold promise for treating leishmaniasis, a parasitic infection that many consider one of the world’s most overlooked diseases. The findings are available online today in PLoS Neglected Tropical Diseases.
These drug candidates, which are able to disrupt the growth of a certain stage in the life cycle of the parasite, were found by screening nearly 200,000 chemical compounds and then regrouping them into chemotypes or chemical classes, both new and known, explained senior investigator John S. Lazo, Ph.D., director of Pitt’s Drug Discovery Institute and Allegheny Foundation Professor in the Department of Pharmacology and Chemical Biology, Pitt School of Medicine. One of the most potent compounds was further tested in a mouse model of leishmaniasis to confirm it could be effective against the infection.
“We are making real progress in our effort to find new drugs to treat what I’d call the most neglected of the neglected diseases,” Dr. Lazo said. “And the method we’ve developed could be applied to find treatments for other parasitic infections, which are an enormous global health burden.”
According to the U.S. Centers for Disease Control and Prevention, each year worldwide, there are about 1.5 million new cases of cutaneous leishmaniasis skin infections, which lead to ulcers, and about 500,000 visceral infections, which lead to fever, weight loss and enlargement of the spleen and liver,. There is no vaccine or drug to prevent the parasitic infection, which is transmitted through sandfly bites.
Interest in developing new treatments for leishmaniasis has grown because of the military presence in Afghanistan and Iraq, where the infection is common, said co-investigator Col. Alan Magill, M.D., director of the Division of Experimental Therapeutics at the Walter Reed Army Institute of Research, Silver Spring, Md.
“Our soldiers are at risk for becoming infected with the Leishmania parasite, but the treatments we have can produce serious side effects,” he said. “Also, the organism is becoming resistant to those agents, which haven’t changed in 50 years.”
For the new study, lead investigator Elizabeth R. Sharlow, Ph.D., a research assistant professor in Pitt School of Medicine’s Department of Pharmacology and Chemical Biology, took unconventional approaches to find drug candidates. First, she developed an assay based on the promastigote, the Leishmania life cycle stage that infects the sandfly, to measure the candidate’s ability to inhibit the parasite’s growth.
“Another unusual step we took was to screen compounds at relatively high concentration, which would make them more likely to affect promastigote growth,” Dr. Sharlow said. “The aim was to maximize the diversity of the active compounds, which we then clustered into similar chemotypes with powerful computational methods to make further testing more manageable.”
The researchers have dubbed this process “HILCES” for high throughput, low-stringency, computationally enhanced small molecule screening. Low stringency is the drug discovery term for high concentration.
A promising anti-leishmanial compound they found turned out to be disulfiram, or Antabuse, a drug that causes an acute sensitivity to alcohol and that is sometimes prescribed to discourage drinking among patients with chronic alcoholism. Testing in a mouse model of the infection showed that it could slow promastigote growth in a living organism, further demonstrating that the HILCES strategy can reveal effective, as well as unexpected, drug candidates.
“In a million years, we wouldn’t have thought about using a compound such as disulfiram for leishmaniasis,” noted Dr. Lazo. “It has appeal because it has already been widely used and is inexpensive, but in its current form, it might not be the best option to treat the infection. We plan to develop it further with our colleagues at Walter Reed to improve the compound’s potency and efficacy.”
All of the primary and confirmation screening data has been made available online, “so it can be data mined by medical researchers and industry anywhere in the world to identify and refine other anti-leishmanial drug candidates,” Dr. Lazo added. “And, the same screening techniques could be invaluable to find compounds to treat other parasitic infections.”
Other co-authors of the paper include David Close, B.S., Tong Ying Shun, Ph.D., Stephanie Leimgruber, M.S., Robyn Reed, M.S., all of the University of Pittsburgh Drug Discovery Institute and the Pittsburgh Molecular Library and Screening Center; Peter Wipf, Ph.D., Pitt Department of Chemistry; Gabriela Mustata, Ph.D., Department of Computational Biology, Pitt School of Medicine; and Capt. Jacob Johnson, Ph.D., Lt. Col. Michael O’Neil, Ph.D., and Col. Max Grogl, Ph.D., all of the Walter Reed Army Institute of Research.
The research was funded by grants from the U.S. Army and the National Institutes of Health.
Source: ScienceDaily (Nov. 10, 2009)
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AIDS Drugs – HIV
Last Updated on Monday, 14 December 2009 05:19 Written by Editor Monday, 14 December 2009 05:19
In the early 1980s, the human immunodeficiency virus (HIV) was identiÂfied as the etiologic agent of acquired immune deficiency syndrome (AIDS). More than 3 million people worldwide died from HIV/AIDS in 2003, according to a July 2004 United Nations report. During the same period, about 5 million people contracted the human immunodeficiency virus, bringing the total number of people living with HIV worldwide to 38 million. Although AIDS was called the «gay men’s disease» at the beÂginning of the outbreak, it was soon discovered that sexual intercourse was not the only way of transmission. Blood transfusions and mother-to-baby transmission also spread the virus.
In comparison to the scourges caused by other viruses in history, we were more prepared and have achieved astonishing milestones against AIDS, thanks to our accumulated knowledge and efforts around the globe. HIV was identified and shown to be the cause of AIDS in less than 2% years. It took only another 2 years for blood tests to become commercially available. In 1987, the first anti-HIV drug, AZT, was introduced. With the arrival of the HIV protease inhibitors and triple drug therapy (the cocktail therapy) in 1995, many patients who would otherwise have died are still alive. In 1996, Time magazine named AIDS researcher David Ho «Man of the Year» for his revolutionary idea of the cocktail therapy.
Who discovered HIV was such a contentious isÂsue that it took the President of the United States and the Premier of France to settle the dispute.
In 1983 Francoise Barre-Sinoussi and Luc Montagnier, in the laboratory led by Montagnier at the Institut Pasteur de Paris, first detected and later isoÂlated a retrovirus, lymphadenopathy-associated virus (LAV), which they believed was the cause of AIDS. During their research on the virus, Montagnier’s labÂoratory collaborated with Robert C. Gallo, a renowned virologist at the National Cancer Institute (NCI), who was one of the most widely referenced scientists in the world in the 1980s and 1990s. Montagnier and Gallo frequently exchanged virus sampies and information. In April 1984, Gallo held a press conference anÂnouncing that his laboratory had isolated a retrovirus, human T-lym-photrophic virus (HTLV-III), that he believed to be the cause of AIDS. Gallo was basking in scientific glory and was widely considered a leading contender for the Nobel Prize. Soon it was confirmed that Gallo’s HTLV-III and Montagnier’s LAV were identical. In 1986, a nomenclature comÂmittee was set up, chaired by Harold Varmus, an expert in avian retrovirus and then director of the NIH. The NIH committee settled on the name of human immunodeficiency virus (HIV).
In April 1984, Gallo’s laboratory filed a patent on an HIV blood test kit using his HTLV-IIIB-ELISA (enzyme-linked immunosorbent assay), which was issued in a record 13 months via a special category involving naÂtional security. Although Institut Pasteur had filed a patent in the United States much earlier, in December 1983, it was not granted until a later date. Gallo’s HIV test kit was approved by the FDA in 1985. An acrimonious leÂgal battle ensued for the priority of the discovery of the HIV between the French and American teams. The contentious scientific and legal controÂversies came to an end in March 1987 when a historic agreement was signed by the directors of the NIH and the Institut Pasteur and ratified by Ronald Reagan and Jacques Chirac. The patents would become the joint properties of the two institutions, which would share the royalties. The three inventors from the NIH, including Gallo, would receive $100,000 annually from the royalties earned.
Even the intervention by two heads of state did not put the matter to rest. In November 1989, a Pulitzer Prize-winning investigative reporter, John Crewdson, published a 50,000-word article in the Chicago Tribune on the Montagnier-Gallo priority dispute. He concluded that Gallo had either stolen or allowed his samples to be contaminated with Montagnier’s virus. The controversy generated resulted in congressional investigations. In the end, it was found that Mikulas (Mika) Popovic from CzechoslovakÂia, a cell biologist in Gallo’s laboratory, had isolated HTLV-III from a pool by mixing several blood samples from different sources, including Montagnier’s sample, which contained LAV. Pooling blood samples was an unusual practice in virology. In 1991, Gallo admitted in Nature that he had not discovered the new virus. In 1996, he left the NCI, where he had worked for 30 years, to become the director of the Institute of HuÂman Virology at the University of Maryland Biotechnology Institute in Baltimore.
In 1987, the first anti-AIDS drug, AZT, was introduced by Burroughs Wellcome. AZT, which blocks HIV reverse transcriptase activity, stands for azidothymidine, with the generic name of zidovudine and the trade name of Retrovir. Popular media often give the credit to Gertrude Elion of Burroughs Wellcome for having discovered AZT. In fact, alÂthough Elion and George Hitchings (see chapter 1, page 19) developed the concept of using nucleotides as antimetabolites in treating cancers, AZT itself was synthesized by a group led by Jerome Horowitz of the Detroit Institute of Cancer Research in 1964 as a possible anticancer drug. Horowitz, now a professor at Wayne State University, published his synÂthesis as a note in the. Journal of Organic Chemistry in 1964.
Since its birth, AZT had a checkered life as a drug looking for a disease to treat. AZT did not show efficacy in treating cancers; the drug also failed to prolong the lives of leukemic animals. In 1974, a German laboratory found it effective against viral infection in mice—Wolfram Ostertag of the Max Planck Institute for Experimental Medicine showed that leukemia helper virus (LLV-F) replication by AZT occurred via phosphorylation of AZT to the corresponding triphosphate, which cannot be incorporated into the growing strand of DNA. Ostertag correctly concluded that AZT-triphosphate worked by binding to the growing strand of DNA. BurÂroughs Wellcome acquired AZT and explored the possibility of using it to treat the herpes virus under the guidance of Gertrude Elion, although it did not make it to the market.
In 1984, shortly after Gallo announced his discovery of the retrovirus, HTLV-III, the head of the NCI, Samuel Broder, organized a team to screen antiviral agents as possible treatments for AIDS. In all, more than 50 pharmaceutical companies submitted their possible antiviral drug canÂdidates to Broder’s team for screening. Together with Dani Bolognesi, an AIDS researcher at Duke University, Broder obtained some of the potenÂtial antiviral compounds from Burroughs Wellcome. In February 1985, usÂing an assay developed by Hiroaki «Mitch» Mitsuya, AZT was found to be active in vitro in the NCI laboratories in Bethesda. Wellcome patented AZT as an antiviral drug in June 1985 and promptly commenced the cliniÂcal trials. As with cancer drugs, the Phase I trials for AIDS drugs are done with patients rather than with healthy volunteers. The first trials to test AZT in patients with HIV showed dramatic efficacy. For ethical reasons, the company terminated the trials and switched patients on placebo to AZT immediately. The FDA approved the use of AZT on March 19,1987, within 22 weeks. The recommended dose was one 100-mg capsule every 4 hours around the clock. Thus AZT established itself as the first antiviral drug in the arsenal against HIV. The mechanism of action of AZT is the blockade of the HIV reverse transcriptase activity. Reverse transcriptase, first isolated by David Baltimore and Howard Termin in 1970, is the enÂzyme that transcribes RNA into DNA. The success of AZT incited the deÂvelopment of many nucleotide anti-HIV drugs in an effort to minimize the toxicities that AZT displayed.
Among the newer reverse transcriptase inhibitors, Ziagen represents a vast improvement over AZT, a nucleotide whose gycosidic core structure is metabolized rapidly. Whereas AZT has to be taken every 4 hours around the clock, Ziagen allows a twice-daily regimen. When the oxygen on AZT is replaced with a methylene group, carbocyclic nucleoside analogs such as Ziagen are metabolized much more slowly by the body. Ziagen was develÂoped by Glaxo Wellcome (now part of GlaxoSmithKline) using a technolÂogy developed by Robert Vince of the University of Minnesota, who licensed the patent to Glaxo Wellcome in 1993.
Robert Vince is a professor of medicinal chemistry and director of the Center for Drug Design at the University of Minnesota. After completing his Ph.D. training in 1966, he began his independent research in the field of antiviral medicine. In the mid-1970s, he designed an antiviral comÂpound, carbocyclic Ara-A (cyclaradine), that was more effective in comÂbating herpes virus than acyclovir was. Because he did not patent his discovery, it was difficult to entice the pharmaceutical industry to develop it. That experience taught him a lesson on the importance of intellectual properties. In the mid-1980s, inspired by the success of AZT, Vince started to tinker with nucleosides as HIV reverse transcriptase inhibitors. In retrospect, it was logical for him to replace the oxygen on the nucleoÂsides related to AZT with a methylene group in order to improve bioavail-ability. But at that time, it represented a significant improvement. Along with a visiting researcher from China, Mei Hua, he synthesized a group of carbocyclic nucleoside analogs, which they called carbovirs. The NIH tested the carbovirs and found them to be the most active compounds in their screen against HIV since AZT. In fact, the carbovirs were the first compounds found active against HIV that were specifically synthesized for that purpose. In 1987, the University of Minnesota patented their synthesis and a group of antiviral drugs, listing Vince and Hua as coin-ventors. The university subsequently licensed the patent to Glaxo Well-come, which arrived at Ziagen by substituting a propyl cyclopropyl group for the purine ring using the synthetic route developed by Vince. Because of Ziagen’s favorable pharmacokinetics profile, it allows a twice-daily regÂimen and has brought in hundreds of millions of dollars in sales for the company.
The credit for any important discovery often seems to be a contentious issue. In this case, the stakes were high, as both AIDS and a large sum of money were involved. Glaxo claimed that Ziagen was not covered by the Vince-Hua patent because the patent did not cover Ziagen per se, whereas Minnesota contested that alkyl surely included cyclopropyl. In October 1999, the University of Minnesota and Glaxo settled this dispute, and as part of the settlement Glaxo agreed that the University patents were valid and enforceable. The settlement brought a financial windfall for MinÂnesota and the inventors. With the Ziagen money, estimated at $250 milÂlion thus far, Minnesota established a Center for Drug Design, with Vince as its director. Vince is putting his share of the Ziagen money to work on potential new AIDS drugs and other potential antiviral and anticancer agents at the center.
In addition to AZT and Ziagen, many HIV reverse transcriptase inÂhibitors exist. An organic chemistry professor at Emory University, Dennis Liotta, and his virologist colleague, Raymond Schinazi, discovered another reverse transcriptase inhibitor 3TC (lamivudine, Epivir), which allows a once-daily regimen. BMS’s d4T was licensed from Yale University. The drug gained international fame when activists at Yale persuaded the uniÂversity to rewrite a license agreement with BMS so that generic d4T could be sold in South Africa. BMS’s ddl was approved in mid-1991, and nevi-rapine (trade name Viramune) by Boehringer Ingelheim was approved by the FDA in June 1996.
Posted under HIV Research, New Drugs, Press Releases | Comments Off
NightSHADE – The Dedicated In Vivo Plant Imager – a New Concept for Plant Research
Last Updated on Monday, 7 December 2009 11:59 Written by Editor Monday, 7 December 2009 11:59
Bad Wildbad, Germany, November 30, 2009 / b3c newswire / – Based on the experiences with the NightOWL in vivo imager Berthold Technologies has developed the new NightSHADE imaging system with plant research in mind.
For applications such as gene research, circadian rhythms, regulation of plant growth, stress tolerance and drug screening the NightSHADE will offer unique features for plant research.
• Top-view emCCD camera with high resolution
• LED-based plant illumination with daylight simulation
• 2nd camera for side-view imaging
• x-y table and rotating table for 360° viewing
• temperature & humidity control
Caption: NightSHADE in vivo plant imager
NightSHADE is equipped with a highly sensitive 1 Mpixel emCCD camera cooled to an absolute tem-perature of -20 °C. The electron multiplying (em) mode of the camera enhances the signals by amplifying the electrons during readout. This increases the sensitivity with short exposure times and enables single photon detection. The maximum quantum efficiency is reached between 550 and 750 nm making the camera an ideal choice for luciferases and fluorescent dyes:
Caption: NightSHADE is equipped with a 1 Mpixel emCCD camera, an ideal choice for luciferases and fluorescent dyes.
Various accessories like filters, transilluminators or the mobile workstation are available. With the certified calibration you can check easily the performance.
Link to the news release and high resolution pictures
About Berthold Technologies – www.berthold.com
Berthold Technologies, a family driven company with it’s headquarters in Bad Wildbad, Germany, has been providing bioanalytical instruments to the research and the diagnostic market for more than 60 years. The company is offering innovative products through a worldwide network of subsidiaries and distributors to customers in academic and pharmaceutical research as well as clinical diagnostics.
Contact
Bettina Felletschin
BERTHOLD TECHNOLOGIES GmbH & Co.KG
Calmbacher Str.22
75323 Bad Wildbad
Germany
Phone +49-7081-177-0
Fax  +49-7081-177-100
bio@Berthold.com
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Glycotope receives regulatory approval for GlycoExpressTM Technology and initiates first clinical trial with lead antibody GT-MAB 2.5-GEX TM
Last Updated on Monday, 7 December 2009 11:57 Written by Editor Monday, 7 December 2009 11:57
Berlin, Germany, November 25, 2009 / b3c newswire / - Glycotope GmbH, a leading German Biotech company, has received regulatory approval by Germany and Italian regulatory authorities for a Phase I study of Glycotope´s lead antibody GT-MAB 2.5-GEXTM for the treatment of various solid cancers. The approvals further underline the suitability of Glycotope´s proprietary GlycoExpressTM technology for the improvement, glycooptimization and high yield production of therapeutic proteins for the use in humans.
“The approval of GT-MAB 2.5-GEX as well as the regulatory approval of the GlycoExpress production technology based on its glycoengineered human cell lines represents a significant milestone for the company†says Steffen Goletz, PhD, Founder, CEO and CSO of Glycotope. “After generating very encouraging data in pre-clinical studies, we are now looking forward to demonstrate the importance of glycosylation in the clinic by generating a substantial benefit to patients.â€
The Phase I study will evaluate the safety and tolerability of GT-MAB 2.5-GEXTM in a broad series of cancer indications.
Link to the news release
About GT-MAB 2.5-GEX
GT-MAB 2.5-GEXTM is a novel, exceptionally potent monoclonal antibody for the treatment of a broad variety of cancer indications. The antibody is directed against a novel tumor-specific combined carbohydrate-protein epitope present in a large number of patients of various cancers. GT-MAB 2.5-GEXTM shows three highly effective key modes of anti-tumor action: ADCC, phagocytosis and induction of apoptosis with an exceptionally high and specific tumor accumulation and tumor killing already at doses as low as 0.5 mg/kg. Â
The antibody’s fully human glycosylation is optimized to yield a largely improved ADCC activity, bioavailability and no non-human immunogenic carbohydrate structures. This was achieved by Glycotope´s proprietary technology platform GlycoExpress TM, a screening and high yield production system of glycoengineered human cell-lines that allows significant enhancement of therapeutic potency by optimizing a protein’s glycosylation in various aspects.
About Glycotope GmbH
GLYCOTOPE was founded in 2001 and focuses on the improvement and humanization of glycosylation structures on proteins, a comparatively new field in biotechnology. GlycoExpressTM, the company’s proprietary technology permits making existing and new drugs more effective and tolerable in the human body, which is of considerable medical as well as economic importance. The current product range currently includes both proprietary antibodies for cancer therapy (e.g. GT-MAB 2.5-GEX TM) and significantly improved versions (2nd generation) of antibodies and other therapeutic proteins already on the market.
Posted under Cancer Research, Press Releases | Comments Off
AnaSpec Introduces α & β -Synuclein Recombinant Proteins
Last Updated on Monday, 7 December 2009 11:55 Written by Editor Monday, 7 December 2009 11:55
AnaSpec has announced the release of two new recombinant proteins, ï¡-synuclein (SNCA) and ï¢-Synuclein (SNCB). These proteins, along with ï§-synuclein (SNCG), are members of the synuclein family of small proteins expressed primarily in neural tissue and in some tumors.1 Synuclein proteins, found only in vertebrates, possess a highly conserved N-terminal domain, with a variable number of 11-residue repeats and a less conserved C-terminal, with a preponderance of acidic residues.1
ï¡-Synuclein
ï¡-Synuclein is an abundant protein of 140 residues that is present in high concentration at presynaptic terminals and is found in both soluble and membrane-associated fractions of the brain. Several possible functions have been suggested, among which are vesicle release and trafficking. In vitro incubation in the presence of salt (i.e. 0.1M NaCl) with agitation causes ï¡-Synuclein to form fibrils.2-6 ï¡-Synuclein, labeled with AnaSpec’s proprietary green dye, HiLyte Fluorâ„¢ 488 (Ex/Em=503/525 nm) is also available.
ï¢-Synuclein
N-terminal of β-synuclein is highly homologous to α-, γ-synucleins and consists of degenerative “KTKEGV†repeats.7-10 Similar to α-synuclein, beta-synuclein is found primarily in the brain; however, it does not associate with Lewy bodies in Parkinson disease like α-synuclein.7-10 Beta-synuclein was found to inhibit production of phosphatidic acid by the phospholipase D2 transmembrane protein in vitro.7 In addition, β-synuclein was detected in many breast and ovarian tumors.7 Recent investigations demonstrated that β-synuclein can induce mild experimental autoimmune encephalomyelitis (EAE) in Lewis rats.8
References
-
George, JM. Genome Biol. 3, reviews 3002.1 (2002).
-
Trojanowski, JQ. & VM. Lee, Ann. N. Y. Acad. Sci. 991, 107 (2003).
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Masliah, E., et al. Science 287, 1265 (2000).
-
Van Der, P. H, et al. J. Neurosci. 20, 6021 (2000).
-
Feany, MB. & WW. Bender, Nature 404, 394(2000).
-
Weinreb, P. H., et al. Biochemistry 35, 13709 (1996).
-
Rivers, R.C. et al. Protein Sci 17, 887 (2008).
-
Sung, Y-H. et al. Protein Sci 15, 1162 (2006).
-
George, JM. Genome Biol 3, 3002.1 (2001).
-
Bruening, W. et al. Am Cancer Soc 88, 2154 (2000).
-
Kela-Madar, N. et al. J Neuroimmunol 208, 19 (2009).
About AnaSpec
AnaSpec is a leading provider of integrated proteomics solutions to the world’s largest biotech, pharmaceutical, and academic research institutions. With a vision for innovation through synergy, AnaSpec focuses on three core technologies: peptides, detection reagents, and antibodies.
AnaSpec recently joined forces with Eurogentec to provide an even broader spectrum of products and services to serve the worldwide life science community.
For more information visit www.anaspec.com
About Eurogentec
Eurogentec is a leading global supplier of innovative reagents, kits, specialty products and custom services to scientists in the life science, biotechnology, pharmaceutical and diagnostic markets. Eurogentec provides a wide range of expertize in small- and large-scale DNA, RNA, PCR and qPCR kits, peptide synthesis and antibody supply for research applications. Our ISO13485:2003-certified manufacturing facilities in Belgium provides a wide range of high value oligonucleotide-based components for diagnostic and therapeutic applications. Eurogentec’s Belgium manufacturing facility is complemented by additional production facilities in North America and Japan. Eurogentec is also an experienced Contract Manufacturing Organization (CMO) for Biopharmaceuticals, operating a full-service, state-of-the-art GMP facility in Belgium.
Eurogentec is a privately held company headquartered in Liège, Belgium, with subsidiaries in North America, France, Germany, the UK, the Netherlands and Switzerland and has additional production facilities in North America, Japan and Singapore. Eurogentec employs 400+ people globally.
For more information visit www.eurogentec.com
Contact: Albert Olson Hong
Tel: 510-791-9560 x 243
Email: albertoh@anaspec.com
Posted under Press Releases | Comments Off
SampleScan Plus
Last Updated on Friday, 4 December 2009 11:30 Written by Editor Friday, 4 December 2009 11:26
- Scans one tube in less than one second
- One USB connection
- No power supply needed
- Compatible with Matrix, Micronic, Nunc, Matrical, and ABgene 2D barcoded tubes
- Also decodes 1D barcodes from vials and racks
- Keyboard wedge functionality
- Scans directly into any open application
- PC or Mac compatible
-
Smallest Size:Â 4″ X 4″ X 5.5″
- Introductory List Price:Â $2,295.00
SampleScan Mini – High-Speed Single Rack Reader
- Scans one rack in less than 5 seconds
- Compatible with Matrix, Micronic, Nunc, and ABgene 2D barcoded tube racks
- Single tube scan feature
- Decodes all SBS formats
- Available with 1D reader integration
- LIMS integration ready
- Smallest size:Â 6 1/4″ X 10 1/2″ X 1 1/2″
Posted under New Products, Press Releases | Comments Off
Trana Discovery and Southern Research Institute Find Bioactive HIV Antiviral Compounds: NIAID contracts additional $700,000 to screen 300,000 more compounds for HIV inhibition
Last Updated on Wednesday, 2 December 2009 01:50 Written by Editor Wednesday, 2 December 2009 01:50
Trana Discovery and Southern Research Institute Find Bioactive HIV Antiviral Compounds: NIAID contracts additional $700,000 to screen 300,000 more compounds for HIV inhibition
PRNewswire – October 28, 2009
CARY, N.C. and BIRMINGHAM, Ala., Oct. 28 /PRNewswire-USNewswire/ — Trana Discovery, Inc., an infectious disease drug discovery technology company, and Southern Research Institute, a not-for-profit contract research organization conducting basic and applied preclinical drug research, today announced that several bioactive hits from a set of 15,000 diverse small molecule compounds screened under contract with the National Institute of Allergy and Infectious Diseases (NIAID) exhibit antiviral activity against HIV-1 infected cells. Among the compounds tested at Southern Research using the Trana HIV 201 High-Throughput Screening (HTS) assay, 16 compounds demonstrated inhibition of HIV replication in infected human cells and several of these compounds were judged to be “potentially druggable.”
The screening assay used to identify the compounds is based on the premise that HIV-1 has evolved to use tRNALys3 as a primer for initiation of reverse transcription. Therefore, the interaction between tRNALys3 and viral genomic RNA represents a potential novel target for HIV-1 drug development. The biochemical assay to identify inhibitors of the interaction between tRNALys3 and HIV-1 genomic RNA was developed by Trana and transferred to Southern Research for high-throughput screening. Southern Research converted the assay to a homogeneous amplified luminescent proximity assay using AlphaScreen(R) reagents from PerkinElmer.
During this initial pilot study, 164 compounds were identified from the diversity set library as hits. Of these hits, 136 were retested in dose-response against HIV-1IIIB replication in a CEM-SS cytoprotection assay. Sixteen of this last group of compounds inhibited HIV-1 replication.
“These data indicate that the TRANA Discovery assay has identified a number of compounds with modest antiviral activity against HIV-1,” said Roger Ptak, Co-Principal Investigator, Southern Research Institute, in his report to the Division of Acquired Immunodeficiency Syndrome (DAIDS) within NIAID. “Additional testing of compounds with similar structures, as well as broader HTS, should lead to the identification of lead compounds that inhibit HIV-1 replication through the novel mechanism of inhibiting the interaction between tRNALys3 and viral genomic RNA.”
As a result of this successful pilot study, DAIDS has approved $700,000 of additional funding for the contract with Southern Research Institute in order to screen an additional 300,000 compounds and to conduct confirmatory testing of selected lead compounds. Lead candidates (or analogs) identified through this screening will be pursued by Trana Discovery for development and to secure the property rights and patents as deemed appropriate.
Toward that end, Trana Discovery is seeking organizations interested in licensing identified leads or that hold diverse collections of compounds or compounds with known bioactivity against HIV but unknown mechanism of action to identify candidates for drug development.
The use of high-throughput screening (HTS) assays developed by Trana Discovery can provide licensing opportunities for exclusive rights to new drug classes and reduce the cost and time for drug discovery.
“We are excited about the results from the initial screening efforts and for the confidence exhibited by the NIAID/DAIDS by this additional funding commitment,” said Steve Peterson, CEO of Trana Discovery. “We remain very optimistic that the use of our HIV assay will lead to new antivirals for the treatment of this disease.”
NIAID conducts and supports research to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. The NIAID is a component of the National Institutes of Health (NIH), the primary federal agency for conducting and supporting basic, clinical and translational medical research. Work for this project was performed under the DAIDS, NIAID contract N01-AI-70042; Roger Miller, Project Officer.
The HTS screening was conducted at the Southern Research High-Throughput Screening Center which consists of a suite of laboratories designed for efficient screening of large compound libraries and has the capacity for screening a wide variety of assay types. The Trana Discovery assay was recently validated in a 1536 well format, which increases the screening capabilities to over 100,000 compounds per day.
Organizations interested in licensing the Trana HIV 201 assay should contact Trana at info@tranadiscovery.com or by calling 866-390-3452 (toll free) or +1-919-342-6192. Parties interested in screening compounds using this assay at Southern Research Institute facilities may contact David Harris at d.harris@southernresearch.org or call +1-800-967-6774.
About Trana Discovery, Inc.
Trana Discovery, an anti-infective drug discovery technology company, helps its partners find new classes of drugs for the treatment of serious bacterial, viral, and fungal infectious diseases. Our proprietary assays identify compounds that work through a unique mechanism of action: inhibition of the target pathogen’s ability to use transfer RNA (tRNA) essential for propagation. The use of high-throughput screening assays developed by Trana Discovery will reduce the cost and time for drug discovery. Our assays provide licensing opportunities for exclusive rights to new drug classes. Trana Discovery has licensed the patented technology emanating from 20 years of research conducted at North Carolina State University, and holds patents that expand on this core technology and its use in high throughput screening. The company is located in Cary, North Carolina. For more information, please visit www.tranadiscovery.com.
About Southern Research Institute
Southern Research Institute is a nonprofit 501(c)3 scientific research organization that conducts preclinical drug discovery and development, and advanced engineering research in materials, systems development, environment and energy. Our more than 550 scientific and engineering team members support clients and partners in the pharmaceutical, biotechnology, defense, aerospace, environmental and energy industries. Southern Research is headquartered in Birmingham, Ala., with facilities in Wilsonville, Ala., Anniston, Ala., Frederick, Md., and Durham, NC and offices in New Orleans, La., Washington, DC and Kiev, Ukraine. For more information about Southern Research and its capabilities and accomplishments, visit www.SouthernResearch.org.
*Bilbille Y, et al. Vendeix Nucleic Acids Res. 2009 Jun;37(10):3342-53. Epub 2009 Mar 26. See www.tranadiscovery.com for complete reference.
Source: Southern Research Institute
Posted under Grants and Awards, HIV Research, Press Releases | Comments Off
DiscoveryBioMed Awarded $300,000 NIH Grant for Cystic Fibrosis Drug Research and Development
Last Updated on Wednesday, 2 December 2009 01:35 Written by Editor Wednesday, 2 December 2009 01:35
BIRMINGHAM, Ala. – (Business Wire) DiscoveryBioMed, Inc. (DBM) today announced that it has been awarded a Phase 1 Small Business Innovation Research (SBIR) grant by the National Institutes of Health (NIH). The $308,000 grant will be used to advance certain small molecule drug discovery programs designed to correct the genetic mutation most common to cystic fibrosis (CF). “SBIR funding is an essential part of DiscoveryBioMed’s ability to provide our academic clients with cost-effective access to our world-class drug discovery engine,†said Dr. Erik Schwiebert, Chief Executive Officer of DiscoveryBioMed. “By screening our test drugs on DBM’s proprietary disease-relevant human cell backgrounds, our clients are able to facilitate their basic research, bringing new therapies closer to patients. The SBIR grant announced today is an example of this strategy in action.â€
Dr. Schwiebert continued, “We are particularly pleased that the NIH has chosen to provide funding for this important drug discovery program and we are proud to be partnered with UAB’s Gregory Fleming James Cystic Fibrosis Research Center in the pursuit of new clinical treatments for Cystic Fibrosis.â€
To date, DiscoveryBioMed, along with partners, James Collawn, Ph.D. and Zsuzsa Bebok, M.D., have screened approximately 25,000 compounds as part of this program. As a result of the SBIR award announced today, the team will be able to screen 50,000-70,000 additional compounds. In addition, the collaboration has already yielded the discovery and validation of a panel of 5 lead corrector compounds with nanomolar potency and 10-20 fold greater potency that any existing corrector drugs. Medicinal chemistry derivatives are currently being synthesized from the most potent lead compound from a family of drugs that had common molecular structure. Patent protection is in its final stages with work being facilitated by the UAB Research Foundation.
DBM and UAB investigators have mutual rights to existing and future lead compounds going forward and have contributed equally to the partnership.
“We are extremely pleased to be working with DiscoveryBioMed. Their exceptional technology and excellent small molecule screening library make them an ideal partner for this program, said James F. Collawn, Ph.D., Professor of Cell Biology at UAB. “We look forward to a continued and active scientific collaboration with DiscoveryBioMed.â€
Dr. Collawn continued, “The SBIR grant announced today is a meaningful endorsement of our efforts investigating novel approaches to the development of therapies for the treatment of patients with CF. We believe the human airway epithelial cell model, which was acquired and licensed by DiscoveryBioMed, expressing the mutant CFTR from an endogenous gene is currently the best model for studies of this type. The funds made available through the SBIR grant will allow us to explore new ideas regarding mutant CFTR rescue and may lead to treatment alternatives for CF patients in the near future.â€
The grant announced today is the second to be awarded to DBM this year. The previous award, announced in September, was a Phase 2 SBIR grant to continue research into the discovery and development of small molecules to alleviate multiple chronic human diseases.
About DiscoveryBioMed, Inc.
DiscoveryBioMed, Inc. is a life sciences and biotechnology company that engages in R&D and services work in cell engineering and production and cell-based drug discovery. The company is located within Innovation Depot in Birmingham. Using physiologically relevant cell culture models preferably derived from normal and diseased adult human cells and tissues, it focuses on finding therapeutic compounds for a variety of human diseases. It also applies this custom human cell-based approach to its “fee-for-service†support to researchers in allied areas and currently serves clients both locally in Alabama as well as in 11 other states in the US currently. For more information, visit the DBM website at www.discoverybiomed.com.
Discovery BioMed, Inc.
Erik Schwiebert, Ph.D., 205-307-6535 x 1
erik@discoverybiomed.com
or
Red Mountain Communications
Jonathan M. Nugent, 205-566-3026
jnugent@redmtncom.com
Source: earthtimes.org
Posted under Grants and Awards, Press Releases | Comments Off
Scientists hope mouse research leads to new anti-cancer therapies
Last Updated on Wednesday, 2 December 2009 12:28 Written by Editor Wednesday, 2 December 2009 12:28
Recent collaborative work between Cambridge, Mass., research institutes has discovered a method of screening for chemicals that selectively kill breast cancer stem cells in culture and in mice, a breakthrough that may directly or indirectly lead to new anti-cancer therapies.
“One of the major difficulties with developing good anti-cancer drugs is that the anti-cancer drugs don’t cure the tumors, and part of the reason they don’t cure the tumors is that they’re not very effective in specifically attacking and eliminating the cancer stem cells,†said Dr. Robert Weinberg, founding member of the Cambridge-based Whitehead Institute and a biology professor at MIT. “We’re trying to develop techniques to understand what creates cancer stem cells and how they are perpetuated.â€
A theory prevalent amongst many researchers suggests that the aggressive subset of cancer cells — called cancer stem cells — drives tumor growth and causes tumors to regenerate after chemotherapy has killed 99 percent of their cells.
Isolating true-to-form cancer stem cells proved to be a challenge until recently, when researchers at Weinberg’s lab at the Whitehead Institute discovered a method to manipulate these cells.
The discovery allowed a team of scientists led by Dr. Piyush Gupta of the Cambridge-based Broad Institute to derive cell lines from human breast epithelial cells and use them to screen 16,000 chemicals in culture dishes. The scientists found that 32 of these chemicals specifically target cancer stem cells and kill them.
Gupta’s team then tested the chemical compounds in mice, and narrowed the results down to one chemical, salinomycin, that appeared to shrink tumor growth. The study was published in an August issue of the journal Cell.
“Ours was really the first step in a long process.†Gupta said. “We have one compound now, and it is not clear whether this one compound is ideal in terms of its activity and also in terms of its toxicity.â€
The discovery of the potent chemical does not necessarily mean that it will have any improvement over current cancer treatment. Gupta’s team has started the extensive follow-up testing that is necessary to determine in which stage eliminating cancer stem cells would be most beneficial to patients, and whether the compound is suitable for humans at all.
“Things sometimes appear very promising in pre-clinical studies but then in patients they may for whatever reason not work as well,†Gupta said. “All we can do is try to design the best possible preclinical studies in the hope that it will work in the patients. We really want to understand how the compounds work in animals before we even think about putting them in people.â€
Still, the new screening method is a promising development in the field of anti-cancer treatment. Gupta said he expects some cancer stem cell-targeting therapies to make into human trials within three to five years.
“For a while it seemed like these cancer stem cells were exciting, but there was very little known about them,†Gupta said. “Now I think that we’re finally at the stage where we can really start to understand what’s going on inside these cells.â€
Wicked Local Cambridge
Source: tauntongazette.com
Posted under Cancer Research, Compound Screening, Discoveries, Innovations and Patents, Oncology Research, Press Releases | Comments Off
PharmaGap Reports That GAP-107B8 Showed Strong and Consistent Anti-Cancer Activity in a Wide Range of Cancers in NCI Test
Last Updated on Wednesday, 2 December 2009 12:26 Written by Editor Wednesday, 2 December 2009 12:26
OTTAWA, ONTARIO, Oct 27, 2009 (MARKETWIRE via COMTEX) —-PharmaGap Inc. (TSX VENTURE: GAP)(OTCBB: PHRGF) (“PharmaGap” or “the Company”) is pleased to announce highly positive results from the United States National Cancer Institute (“NCI”) 5-dose in vitro anti-cancer screen of PharmaGap drug GAP-107B8. These results confirm and extend results announced in August from the single-dose study and provide definitive independent validation of GAP-107B8 as an active pharmaceutical ingredient against a wide range of cancers.
GAP-107B8 is a novel peptide protein kinase inhibitor that was designed to specifically target molecular signaling pathways in cancer cells. Targeted therapies are designed to target cancer cells while sparing surrounding normal, healthy, cells, thus causing less toxic effects than many standard chemotherapeutic agents currently in use.
Within a dose concentration range of 10 to 100 micromolar (u M), GAP-107B8 caused 100% growth inhibition (measured against cancer cell growth in untreated groups) in 51 of 56 cancer cell lines and caused at least 50% cancer cell death (measured against the number of cancer cells at the beginning of the test period) in 29 of 56 cancer cell lines.
The standard NCI test methodology generates three values that are used to measure the drug compound’s activity against the cancer cell-line panel. These are: the GI50, the dose that causes an average 50% growth inhibition in the cell lines; the TGI, the dose that causes an average 100% growth inhibition in the cell lines; and the LC50, the dose that causes an average 50% cell death in the cell lines. For GAP-107B8, the GI50 was determined to be 23 u M, the TGI was 51 u M, and the LC50 was 89 u M. These data provide a very clear range of focus for all future studies.
These results provided a large amount of data, from the NCI testing which will be used by the Company to select specific cancer types and to determine an optimum dosing range for future animal studies and subsequent clinical trials. Based on these and prior results, the Company will be focusing its immediate development program on ovarian cancer and melanoma. The first of these animal studies is currently underway at the Ottawa Hospital Research Institute (“OHRI”) in ovarian cancer. Further testing of GAP-107B8 on melanoma is about to commence under the guidance of Dr. Gary Schwartz at Memorial Sloan Kettering Cancer Center in New York. GAP-107B8 showed a strong effect in both melanoma and ovarian cancers in both single-dose and 5-dose testing at the NCI. In addition, the Company and NCI staff will meet in late November to discuss these results and ways in which the NCI may participate in various aspects of the development program for GAP-107B8.
The results across such a wide range of cancer cell lines, including a number which are known to be resistant to standard chemotherapy, indicate that GAP-107B8 has the potential to become a new cancer drug with less toxic side effects than common chemotherapeutic regimens.
Robert McInnis, President of the Company, stated “We are very pleased with the extent of activity in the NCI panel, as this activity against all cell lines provides a wide range of development opportunities for us, and provides us with additional support for a focus on ovarian cancer and melanoma. Our objective of the testing at the NCI – independent and verifiable validation of activity – has been fully realized. Over the past 12 months we have made significant progress in moving our lead drug to clinical trials: generating quality- controlled gram-scale production of the compound; achieving verifiable independent validation of compound activity at both the NCI and here in Ottawa at the OHRI; and programs underway in the area of bioassay development, understanding of signalling pathways involved, and continued testing programs at Memorial Sloan Kettering. This progress is very encouraging to me and to our team. Most importantly, results so far indicate a potential for new hope for the future of patients suffering from several types of cancer”.
About The National Cancer Institute
The National Cancer Institute (NCI), located in Bethesda, MD is an institute of the National Institutes of Health, the primary U.S. Federal Agency for conducting and supporting medical research. The NCI has a mandate to select and screen novel drug compounds that could potentially make a material difference in the “war against cancer”. Selection to the NCI screening program is through a competitive application process. Details on the NCI’s compound screening program can be found at http://dtp.nci.nih.gov/. More general information on the NCI is found at www.cancer.gov.
About PharmaGap Inc.
PharmaGap Inc. (TSX VENTURE: GAP)(OTCBB: PHRGF), based in Ottawa, ON, is a biotechnology company with a core focus on developing novel peptide therapeutics for the treatment of cancer. PharmaGap’s GAP-107B8 is a novel peptide drug designed to inhibit the activity of protein kinase C (PKC), a cell signalling enzyme implicated in certain types and stages of cancer. Independent peer-reviewed research has demonstrated that over-expression of PKC plays a role in the development of many cancer types. For more information please visit www.pharmagap.com.
Note: Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release. No Securities Commission or other regulatory authority having jurisdiction over PharmaGap has approved or disapproved of the information contained herein. This release contains forward looking statements that may not occur or may change materially.
Contacts: PharmaGap Inc. Robert McInnis President & CEO 613-990-9551 bmcinnis@pharmagap.com www.pharmagap.com
SOURCE: PharmaGap Inc.
Posted under Cancer Research, Discoveries, Innovations and Patents, FDA News, New Products, Oncology Research, Press Releases | Comments Off
Aeolus Drug Protects the Gastrointestinal Tract in Acute Radiation Syndrome Studies Sponsored by the National Institutes of Health`s National Institute for Allergy and Infectious Diseases
Last Updated on Wednesday, 2 December 2009 12:12 Written by Editor Wednesday, 2 December 2009 12:12
* AEOL 10150 Effectively Increases Regeneration of GI Stem Cells and Reduces the
Severity and Duration of Diarrhea
* Drug Improves Survival When Administered 24 Hours after Total Body
Irradiation
MISSION VIEJO, Calif.--(Business Wire)--
Aeolus Pharmaceuticals, Inc. (OTCBB: AOLS) announced today that recent
experiments in preclinical models conducted by the National Institutes of
Health`s (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
Radiation/Nuclear Medical Countermeasure Development program have shown that
AEOL 10150 can effectively increase regeneration of gastro-intestinal (GI) stem
cells, reduce the severity and duration of diarrhea and improve survival when
administered at 24 hours after doses of total-body irradiation that produce the
lethal GI syndrome. There are no published studies of agents that accomplish
this enhanced stem cell regenerative effect while maintaining GI function and
improving survival when administered post irradiation.
"The Aeolus drug AEOL 10150 passed our first phase of rigorous testing and
showed definitive effects on crypt stem cells and other secondary parameters
used to assess drug efficacy in ameliorating the acute GI syndrome," stated
Catherine Booth, Ph.D., Managing Director, Contract Research Services at
Epistem, Ltd. "This is one of few drugs shown to affect 'both' stem cell crypt
regeneration and survival in a syndrome that heretofore has been resistant to
mitigation with drugs administered at 24 hours post lethal exposure."
NIAID has a contract with the University of Maryland to provide product
development support services for the development of countermeasures against
radiation exposure. These studies are being conducted by Epistem, a
subcontractor of the University of Maryland, in compliance with criteria of the
FDA that are a pre-requisite for movement of the Aeolus drug along the pathway
for FDA licensure to treat lethally irradiated persons in the event of a
terrorist nuclear act. Epistem operates a major contract research organization
and provides services to identify novel drugs that can protect or improve the
repair of the gastrointestinal (GI) tract following exposure to irradiation and
performed these studies as part of its US NIH`s program for the screening of a
novel agents for bio-defense applications.
The NIH NIAID Radiation/Nuclear Medical Countermeasure Development program leads
the U.S. effort to develop treatments for radiation sickness following a nuclear
terrorist attack. GI-ARS is a massive, currently untreatable, problem following
high-dose, potentially lethal radiation exposure. Agents that mitigate these
effects would reduce sickness and hopefully prevent fatalities. The tests
performed by NIH/NIAID are also likely to identify agents with oncology
supportive care applications - agents that will reduce the severe ulceration and
diarrhea (mucositis) experienced by patients during radio- and chemo-therapy.
Risk of injury to the intestine is dose-limiting during abdominal and pelvic
radiation therapy-interventions that limit post-irradiation intestinal
dysfunction would have significant impact in large number of patients, estimated
to be between 1.5 to 2 million cancer survivors with post-irradiation intestinal
dysfunction. AEOL 10150 has previously demonstrated protective effects in
protecting healthy normal cells from damage occurring due to cancer radiation
therapy in preclinical models.
Radiation Damage to the GI Tract
The intestinal epithelium, a single layer of cells lining the surface of the GI
lumen, is responsible for vital functions of nutrient absorption, maintaining
fluid and electrolyte balance and protection of the body from bacteria,
bacterial toxins and non absorbed materials. The functional integrity of the GI
system is maintained via incessant production of epithelial cells from
specialized stem cells located in crypts at the base of the epithelium.
High-dose, total-body irradiation can result in a lethal GI syndrome that
results in significant morbidity and mortality within days consequent to killing
of the crypt stem cells and loss of the protective and absorptive epithelial
barrier. There are no FDA-approved drugs or biologics to treat the acute GI
syndrome.
About AEOL 10150
AEOL 10150 is a small molecule that catalytically consumes reactive oxygen and
nitrogen species (free radicals). The compound is a manganoporphyrin that
contains a positively-charged manganese metal ion that is able to accept and
give electrons to and from reactive oxygen species ("ROS") and reactive nitrogen
species ("RNS"). Research has shown that ROS and RNS have important cell
signaling roles, and through its interaction with RNS and ROS, AEOL 10150
appears to have multiple mechanisms of action including anti-oxidant,
anti-inflammatory and anti-angiogenic activities. In preclinical studies AEOL
10150 has demonstrated reductions in the markers for tissue hypoxia,
angiogenesis, inflammation and oxidative stress. Specifically, AEOL 10150 is
able to down-regulate oxidative stress and severe inflammation, which is
responsible for much of the tissue destruction that occurs as a result of
radiation exposure.
AEOL 10150 offers several unique advantages as a countermeasure for the
treatment of ARS, mustard gas and chlorine gas for civilian and military
populations. These include:
-- Flexible Treatment Paradigm - AEOL 10150 is intended for the treatment of
patients post-exposure, even in those who are already exhibiting symptoms,
eliminating the need for immediate administration in a predefined treatment
window. This approach has the added benefit of not requiring biodosimetry (a
means of laboratory analysis of the blood to determine the level of radiation
exposure).
-- Advanced Development Stage - AEOL 10150 has demonstrated safety in three
human clinical trials, and has an extensive pre-clinical safety and toxicology
package completed. The product also has an established stability profile that
permits long-term storage.
-- Large scale manufacturing - Aeolus has contract capacity with a large
manufacturing site to mass produce large quantities of AEOL 10150 under GMP
conditions.
-- Multiple Applications - AEOL 10150 has demonstrated protective effects
against radiation and mustard gas exposure, and within these indications has
shown the ability to treat multiple organ systems.
-- Commercial Application - Additionally, AEOL 10150 is being developed for use
as an adjunct to cancer radiation therapy, and preclinical data suggest that the
compound protects healthy normal cells from the effects of radiation without
compromising the efficacy of the radiation in killing tumor cells.
Potential for AEOL 10150 as a Countermeasure Against Multiple Terrorist Threats
AEOL 10150 has shown significant protective effects against radiation and
mustard gas in preclinical models. Additionally, based on its mechanism, it is
believed that the compound may potentially protect against exposure to chlorine
gas. Studies have been initiated to further explore AEOL 10150`s ability to
protect the lungs from damage due to exposure to mustard gas and chlorine gas. A
compound with the potential to protect against multiple threats would be of
significant benefit in both the military and civilian efforts to protect
citizens against potential threats. The FDA has a special rule under which
compounds may be approved for use against chemical and nuclear threats on the
strength of preclinical efficacy studies, which allows the potential for an
accelerated approval path versus conventional pharmaceutical applications.
About Aeolus Pharmaceuticals
Aeolus is developing a variety of therapeutic agents based on its proprietary
small molecule catalytic antioxidants, with AEOL 10150 being the first to enter
human clinical evaluation. AEOL 10150 is a patented, small molecule catalytic
antioxidant that mimics and thereby amplifies the body`s natural enzymatic
systems for eliminating reactive oxygen species, or free radicals. Studies
funded by the National Institutes for Health are currently underway evaluating
AEOL 10150 as a treatment for exposure to radiation, mustard gas and chlorine
gas. Additionally, the Company has funded mouse and non-human primate studies
necessary to seek approval of the compound as a treatment to protect and/or
mitigate radiation-induced damage to the lungs for which there are no
FDA-approved drugs. Radiation-induced pneumonits and/or fibrosis are potentially
lethal delayed effects of acute radiation exposure. The ability to control these
delayed consequences will also translate into the clinic and further emphasize
the dual utility of AEOL 10150.
About Epistem, Ltd.
Epistem is a biotechnology company commercializing its expertise in epithelial
stem cells in the areas of oncology, gastrointestinal diseases and
dermatological applications. Epistem develops innovative therapeutics and
biomarkers and provides contract research services to drug development
companies. The Group`s expertise is focused on the regulation of adult stem
cells located in epithelial tissue, which includes the gastrointestinal tract,
skin, hair follicles, breast and prostate. Epistem does not conduct research in
the areas of embryonic stem cells or stem cell transplantation. Epistem operates
three distinct business divisions, Contract Research Services, Novel Therapies
and Biomarkers.
Epistem`s Contract Research Services division provides scientific expertise and
preclinical research models to the NIH`s research programme on Radiation/Nuclear
Medical Countermeasure Development. This research programme, funded by the
National Institute of Allergy and Infectious Diseases through a contract with
the University of Maryland School of Medicine, tests drugs from early screening
through advanced development for the prevention and treatment of radiation
sickness following exposure to high dose radiation following a nuclear terrorist
attack. Epistem has developed its proprietary models to provide a unique insight
into the mechanisms of intestinal damage and repair following radiation
exposure. Epistem`s models evaluate the efficacy, mechanism of action, optimal
drug dosing and scheduling of potential new treatments. Epistem has an
eight-year track record of providing testing services to over 130 international
company clients in the United States, Europe, and Japan.
The statements in this press release that are not purely statements of
historical fact are forward-looking statements. Such statements include, but are
not limited to, those relating to Aeolus` product candidates, as well as its
proprietary technologies and research programs. Such forward-looking statements
involve known and unknown risks, uncertainties and other factors that may cause
Aeolus` actual results to be materially different from historical results or
from any results expressed or implied by such forward-looking statements.
Important factors that could cause results to differ include risks associated
with uncertainties of progress and timing of clinical trials, scientific
research and product development activities, difficulties or delays in
development, testing, obtaining regulatory approval, the need to obtain funding
for pre-clinical and clinical trials and operations, the scope and validity of
intellectual property protection for Aeolus` product candidates, proprietary
technologies and their uses, and competition from other biopharmaceutical
companies. Certain of these factors and others are more fully described in
Aeolus` filings with the Securities and Exchange Commission, including, but not
limited to, Aeolus` Annual Report on Form 10-K for the year ended September 30,
2008. Readers are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date hereof.
Aeolus Pharmaceuticals, Inc.
John L. McManus
President and Chief Executive Officer
1-949-481-9825
Source: reuters.com
Copyright Business Wire 2009
Posted under Collaborations, Discoveries, Innovations and Patents, Drug Development, New Products, Press Releases, Research Projects, Stem Cell Research | Comments Off
PharmaGap Advises That NCI Test Results Are Completed and Expected to Be Provided to the Company Shortly
Last Updated on Tuesday, 1 December 2009 01:05 Written by Editor Tuesday, 1 December 2009 01:05
OTTAWA, ONTARIO — 10/20/09 — PharmaGap Inc. (TSX VENTURE: GAP)(OTCBB: PHRGF) (“PharmaGap” or “the Company”) advises that the results of dose-range testing of the Company’s cancer drug GAP-107B8 at the United States National Cancer Institute (“NCI”) can be expected “shortly”. NCI staff has indicated to the Company that testing has been completed and the results can be expected to be received by the Company after analysis and review of these results by the NCI has been completed.The Company announced the results from single dose testing at the NCI on August 24, 2009, which showed significant inhibition of cancer cell growth at a low drug concentration across a wide range of human cancer cells. In this initial single dose test, GAP107B8 demonstrated greater than 50% inhibition in cancer cell growth in 26 of 57 cell lines tested, across all 9 cancer types included in the test panel. The full release can be found on the Company’s website.
The NCI dose range test repeats the single dose test at 5 different dose concentrations across the same cell lines, in order to provide further insights into the drug’s activity at low dose concentrations. With this data, the PharmaGap drug can be compared with the estimated 40,000 drug compounds in the NCI database, using the NCI’s COMPARE software programs, enabling NCI and Company researchers to further understand the drug’s mechanism of action against defined pathways associated with specific cancer types, in order to better define the target cancer or cancers for which application for clinical trials will be made.
Mr. Robert McInnis, President and C.E.O. of PharmaGap, stated that “while we had expected to have the results of this testing in hand earlier, the NCI has indicated that their analysis of the data is proceeding in normal course and will be released to us when that analysis is completed”
About The National Cancer Institute
The National Cancer Institute (NCI), located in Bethesda, MD is an institute of the National Institutes of Health, the primary U.S. Federal Agency for conducting and supporting medical research. The NCI has a mandate to select and screen novel drug compounds that could potentially make a material difference in the “war against cancer”. Selection to the NCI screening program is through a competitive application process. Details on the NCI’s compound screening program can be found at http://dtp.nci.nih.gov/. More general information on the NCI is found at www.cancer.gov.
About PharmaGap Inc.
PharmaGap Inc. (TSX VENTURE: GAP)(OTCBB: PHRGF), based in Ottawa, ON, is a biotechnology company with a core focus on developing novel peptide therapeutics for the treatment of cancer. PharmaGap’s GAP-107B8 is a novel peptide drug designed to inhibit the activity of protein kinase C (PKC), a cell signalling enzyme implicated in certain types and stages of cancer. Independent peer-reviewed research has demonstrated that over-expression of PKC plays a role in the development of many cancer types. For more information please visit www.pharmagap.com.
Note: Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release. No Securities Commission or other regulatory authority having jurisdiction over PharmaGap has approved or disapproved of the information contained herein. This release contains forward looking statements that may not occur or may change materially.
Source: earthtimes.org
Posted under Cancer Research, Drug Development, Press Releases | Comments Off