Archive for January, 2010

AACR-NCI-EORTC conference highlights major expansion in cancer drug pipeline

Last Updated on Monday, 11 January 2010 03:24 Written by Editor Monday, 11 January 2010 03:24

The last decade has seen a major expansion in the cancer drug pipeline and studies are continually underway to advance the arsenal of drugs and create more effective treatments and targeted therapies for patients.

To highlight results of more recent research, the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics International Conference will host a press briefing on “Drugs in the Pipeline.” Sara A. Courtneidge, Ph.D., D.Sc., professor and director of the Tumor Microenvironment Program, and director of academic affairs at the Burnham Institute for Medical Research, will moderate this press briefing.

“Conferences such as the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics International Conference play a very important role in advancing translational cancer research. Here, one can learn about the newest breakthroughs across the continuum of cancer research,” said Courtneidge.

Breakthroughs to date have been made in the development of anti-angiogenesis inhibitors that target the tumor vasculature and of modulators of gene expression and protein stability, according to Courtneidge. Many more agents have been added to the pipeline of cancer drugs, including inhibitors that target the BCR-ABL fusion protein and other kinases. Cytotoxic agents remain a mainstay of cancer therapy, and inhibitors of DNA repair and cancer stem cells show great promise.

The press briefing will take place on Monday, Nov. 16, 2009, from 1:00 p.m. to 2:00 p.m. ET, in Room 202 of the Hynes Convention Center in Boston, Mass.

Reporters who cannot attend in person may call using the following information:

U.S./Canada: (888) 282-7404
International: (706) 679-5207
Access Code: 36170264
Topic: AACR

Leading researchers will present new and exciting data on the role of hsp70 as a novel therapy for breast cancer; various drug compounds that kill leukemia stem cells and yet spare normal stem cells; tolerability results of cediranib for use in children with recurrent or refractory solid tumors; and sensitivity study results of olaparib for colorectal cancer cells containing a specific DNA repair defect.

“This research spans studies on the genetic makeup of cancer cells, validation studies on the roles of key signaling proteins and pathways, the development of novel agents, and the testing of those agents in a variety of pre-clinical and clinical settings,” Courtneidge added.

The following abstracts will be presented during this press briefing:

# B21. Targeting autophagy induced by pan-HDAC inhibitor panobinostat and promoted by acetylated hsp70: A novel therapy for breast cancer

Targeting heat shock response protein with panobinostat, combined with an autophagy inhibitor, is an effective treatment strategy against growing stress cells in breast cancer.

“Clearly this points to a very new approach of targeting heat shock response in combination treatment,” said Kapil Bhalla, M.D., director of the Medical College of Georgia Cancer Center, professor of medicine in the Department of Medicine, Division of Hematology-Oncology at the Medical College of Georgia, and vice president for cancer research at the Medical College of Georgia.

Panobinostat is a potent histone deacetylase (HDAC) inhibitor that has been shown to induce cell death of tumor cell lines, but not the normal cells. In breast cancer cells where programmed cell death is inhibited, pan-HDAC inhibitor treatment induces autophagy, which allows the breast cancer cells to escape elimination.

Bhalla and colleagues evaluated the stress phenotype of breast cancer cells in the mammary fat pad of mice when mediated by two heat shock proteins â€” hsp90 and hsp70, which help to promote cancer survival. The researchers wanted to determine how these inhibitors that deacetylate proteins and histones affect the cell’s function.

“Basically we forced the cancer cell to have autophagy and then pulled the rug from under it by having an autophagy inhibitor take that away,” said Bhalla.

Treatment with panobinostat induced acetylation of amino acid lysine in the hsp70 protein. With growing tumor size they found an increase in hsp70, heat shock response and autophagy.

“Panobinostat accentuates stress, causes autophagy, and sets up the cell to be eliminated by autophagy inhibitors,” Bhalla said.

Panobinostat is not FDA approved for use in breast cancer.
# A51. Identification of compounds targeting human leukemia stem cells

Researchers at the University of Michigan, Ann Arbor, and the University Health Network, Toronto, have found a new paradigm for screening against leukemia stem cells that can target them and spare blood-forming stem cells at the same time.

The researchers identified small molecules, potentially novel or those currently known, that kill leukemia stem cells, but not normal blood-forming hematopoietic stem cells, which are multipotent stem cells that give rise to all blood types. Three of the 10 compounds they studied targeted leukemia stem cells: ciclopirox olamine, etoposide and kinetin riboside.

“Treatment with these compounds, at the appropriate doses, would kill the leukemia cells and potentially minimize blood system side effects, such as anemia,” said Sean McDermott, Ph.D., research investigator in the Department of Internal Medicine, Hematology-Oncology at the University of Michigan Medical School.

In total, the researchers screened a collection of 4,000 small molecules using two novel leukemia cell lines that have properties of leukemia stem cells. Compounds that killed these leukemia cells were further tested on normal hematopoietic stem cells to remove toxic compounds.

“Overall, to find three compounds that target the leukemia stem cell, all with vastly different mechanisms, is extremely surprising and bodes well for future drug discovery efforts,” said McDermott.

Cells from 51 patients with acute myeloid leukemia (AML) and 12 patients with chronic myelogenuous leukemia (CML) were screened with one of the drugs, etoposide. The researchers were surprised by the etoposide results, which showed that the drug may target the leukemia stem cell in 30 percent of patients with AML and 67 percent of those with CML. These patients might benefit from treatment with this chemotherapeutic drug.

“Screening of larger libraries hopefully will identify even more agents for the cancer pipeline,” he added.

Follow-up studies are currently planned for ciclopirox olamine and it would be beneficial in evaluating low-dose etoposide as a single agent. Kinetin riboside may be tested in a clinical setting in the future, according to McDermott.

# A5. Phase I trial and pharmacokinetic study of cediranib in children with recurrent or refractory solid tumors

Results of a new study show that cediranib can be administered safely to children and adolescents with cancer, and that the side effects are tolerable. Preliminary evidence further showed that the drug may have activity in childhood sarcomas.

“There are a number of antiangiogenic agents, like cediranib, in development for adult cancers,” said researcher Elizabeth Fox, M.D., M.S.C.R., staff clinician in the Pediatric Oncology Branch at the National Cancer Institute. “Encouraging results seen in this trial provide a rationale for future clinical trials of cediranib and other antiangiogenic agents in childhood cancer.”

Cediranib is an oral drug that inhibits vascular endothelial growth factor receptor. The recommended dose in adults is 20 mg to 30 mg administered daily every day for 28 days.

Fox and colleagues tested the toxicity and tolerance of this drug when given in 28-day cycles to patients 2 to 19 years old with malignant solid tumors to determine the appropriate dose of cediranib for this age group. Patients who participated in this phase I study had not responded to or recurred after conventional therapy.

Among the 13 patients enrolled, once daily dosing of 12 mg/m2 of cediranib was tolerable. Thus far, three patients have experienced partial shrinkage of their tumor while receiving the antiangiogenic agent. Side effects in children were similar to those seen in adults on cediranib: dose-limiting toxicities were diarrhea, nausea, vomiting, lethargy and high blood pressure.

“This outcome is encouraging and provides evidence that cediranib should be further studied in future clinical trials in young patients with these and other sarcomas to determine the activity of this new agent,” Fox said. “Hopefully, newer classes of anti-cancer drugs currently being developed will have fewer acute and long-term side effects than the chemotherapy that we currently use to treat childhood cancers.”

The researchers are currently evaluating the effects with 17 mg/m2 of cediranib and proposed to the Children’s Oncology Group that a phase II study be conducted in selected childhood solid tumors.

# A114. Preclinical evaluation of the PARP inhibitor olaparib in homologous recombination deficient (HRD) MRE11 mutant microsatellite instable (MSI) colorectal cancer

The investigational cancer therapy olaparib demonstrated activity against colorectal cancer cells, which suggests that microsatellite instable colorectal cancer represents a potential patient population that could benefit from treatment with this agent.

Researchers have already evaluated the use of the oral poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor olaparib and its antitumor activity pre-clinically and in patients with breast and ovarian cancer that contain a specific DNA repair defect in the form of BRCA1 and BRCA2 mutations. These gene mutations are associated with hereditary breast and ovarian cancer and play a major role in the repair of DNA by the homologous recombination repair pathway. PARPs also play a major role in DNA repair, by working in an alternative pathway.

Olaparib exploits the “Achilles’ heel” of homologous recombination deficient cancers by blocking another DNA repair pathway in these already compromised cancer cells, therefore leading to an overload of DNA damage and resulting in tumor cell death. The activity of one such homologous recombination gene, MRE11, is lost as a consequence of microsatellite instability in colorectal cancer cells.

“DNA damage is occurring all the time in our cells and a number of mechanisms have evolved to repair this damage that include the PARP and the homologous recombination repair pathways,” said Mark O’Connor, Ph.D., chief scientist at KuDOS Pharmaceuticals Ltd., United Kingdom.

The aim of this study was to determine if microsatellite instability and MRE11 status correlated with sensitivity to olaparib. Olaparib is an oral anti-cancer drug in early development for the treatment of certain types of breast and ovarian cancer.

The researchers found the majority of colorectal cancer cell lines sensitive to olaparib correlated with microsatellite instability status and had MRE11 mutations. Furthermore, all olaparib-sensitive colorectal cancer cell lines were homologous recombination deficient.

“These results reinforce the idea that PARP inhibition might have broader clinical utility than in BRCA-deficient tumors alone,” said O’Connor. “They support the idea of using targeted cancer therapies in defined molecular genetic backgrounds that exploit specific DNA repair deficiencies in the cancer to be treated.”

http://www.eortc.be/

Source: news-medical.net

Posted under Cancer Research, Drug Development, Oncology Research, Press Releases | Comments Off

Recovery act funds new flu drug discovery center at Washington University

Last Updated on Monday, 11 January 2010 03:20 Written by Editor Monday, 11 January 2010 03:20

Scientists at Washington University School of Medicine in St. Louis are investigating a new way to fight the flu.

They have received funding, largely through the American Recovery and Reinvestment Act (ARRA), to establish a Drug Discovery Center that will look for compounds that enhance the body’s natural virus-killing mechanisms to overcome the flu.

Each year, government agencies work with scientists to develop new flu vaccines to block large-scale flu outbreaks. The vaccines have to be modified yearly because flu viruses constantly change their basic components so the body’s immune system can’t recognize them.

But the Washington University researchers, headed by Michael J. Holtzman, M.D., believe they can identify drugs that enhance the body’s resistance to a large range of respiratory viruses. That means these drugs could prevent or treat many different seasonal flu viruses and the 2009 H1N1 flu virus as well as the common cold virus and other respiratory viruses.

The ARRA provided nearly $2.5 million through the National Institute for Allergy and Infectious Diseases to support this research.

“In past research, we’ve shown that we can defeat flu viruses in mice and in human cells by genetically modifying the interferon-signaling pathway so that it’s more effective in fighting viral infections. So now we are trying to develop drugs that would mimic the effects that we saw in mice and cells,” says Holtzman, the Selma and Herman Seldin Professor of Medicine, director of the Division of Pulmonary and Critical Care Medicine and a pulmonary specialist at Barnes-Jewish Hospital.

Interferon signaling is one of the main ways the body stops virus infections. Interferons secreted by infected cells set off a series of responses that activate virus-attacking immune cells and help stop viral replication. Holtzman and his colleagues found a way to ramp up interferon-signaling mechanisms in mice and protect them from respiratory virus infection.

Then the scientists studied which genes became more active in mice and human cells when they enhanced the interferon-signaling pathway. Now with the new funding, they are taking the next step and building automated systems to look for drugs that replicate the effect of turning on those genes.

“We call it genome-guided drug screening â€” a new method of drug development that is being done in very few places in the world,” Holtzman explains. “We’re putting together a specialized high-throughput system using robotic equipment that can very rapidly screen many different compounds. The system will use high-fidelity cell models and gene expression data to help identify compounds that enhance interferon-signaling mechanisms.”

As part of the project, Holtzman and his colleagues are defining the body’s response to the 2009 H1N1 virus. They are using human airway cells grown in the laboratory to understand why the virus is pathogenic and how its way of infecting its host differs from other viruses.

“The virus has a way of subverting the body’s antiviral response,” Holtzman says. “By analyzing the genes whose activity changes when the virus infects cells, we can find genes responsible for infection and resistance.”

This information will feed into the genome-guided drug screening system to identify drugs effective against the 2009 H1N1 flu virus.

The researchers will also study the role of flu virus infection in the development of asthma and other allergic diseases. They will define what happens in airway cells after infection. By blocking this process with drugs, they hope to stop the development of chronic lung disease that often follows viral infection.

The drug discovery process will begin with compounds that are already approved by the FDA for use in humans, speeding the clinical availability of any drugs that prove effective. While this approach is being established, Holtzman also plans to expand the capabilities of the center in the area of medicinal chemistry so that this group can develop new compounds with increased safety and efficacy that would be beneficial for human use.

Funding from the National Institute of Allergy and Infectious Diseases supports this research.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Source: mednews.wustl.edu

Posted under Drug Development, Press Releases, Swine Flu Research | Comments Off

Developments in Focused Kinase Libraries

Last Updated on Monday, 11 January 2010 03:14 Written by Editor Monday, 11 January 2010 03:14

Chemical libraries have long been a mainstay in the search for new pharmaceutical compounds, and they have been created using many different paradigms. Vast diverse collections of unique compounds have been screened at high throughput to find appropriate effects on target proteins. Such large libraries continue to be used for drug discovery, but screening smaller, more focused libraries, can provide more efficient solutions with better overall hit rates.

Ten years ago, BioFocusÂ®, a Galapagos company, launched a nonexclusive compound library specifically designed to target serine-threonine and tyrosine kinases. This library, SoftFocusÂ® Kinase library one (SFK01), was designed to mimic the binding of ATP to the catalytic (hinge) region and had a rather simplistic design based around an aminopyrimidine core (Figure 1).

Targeting Kinases

Protein kinases are enzymes that phosphorylate substrate proteins at specified residues such as serine, threonine, and tyrosine. The phosphorylation of the substrate protein initiates a cascade, that in turn, modulates the transcription of a gene or set of genes. Kinases play pivotal roles in modulating diverse cellular activities, including growth, differentiation, metabolism, adhesion, motility, and death, and have been implicated as important mediators of certain forms of cancer.

Kinases, therefore, represent key druggable target proteins. The initial realization that most kinases possess highly conserved catalytic domains initially made kinase targets ideally suited for compound screening via focused chemical libraries in which the library compounds were specifically created to bind to the catalytic (hinge) regions.

Despite the slightly higher costs generally associated with the design and synthesis of such focused libraries compared to large and diverse compound collections, true savings can be gained as a result of shortened project cycles coupled with the reduced costs of screening, storage, and quality control of a smaller screening library.

The increasing wealth of structural data available along with a number of new techniques such as in silico design has enabled the continual development of kinase-focused collections, providing increasingly more sophisticated chemical structures. One of the key benefits of this is that the current range of SoftFocus kinase libraries has been designed to target additional binding modes to those involving the hinge region; most notably the DFG-out binding mode and the novel binding mode first observed in the kinase PIM-1.

In Silico Design

Current in silico design processes enable automated docking and scoring of scaffold ideas into a variety of known x-ray structures that have been selected, not only for broad coverage of the kinome, but also different conformational states of individual kinase enzymes. The design premise is that, if the core of the molecule or scaffold contains the key recognition groups for binding into one of the known conformational states, it has the potential to target any kinase.

However, as different side chains or monomers are added, the potential to gain specificity for one target over another becomes reality. The various docking methods used in the design of the BioFocus libraries include hinge binding, the DFG-out model, and novel binding modes.

Hinge Binding

Hinge-binding library designs are validated by docking a minimally substituted scaffold into various different high-resolution kinase x-ray structures. These structures have been selected from across the phylogenetic tree to ensure broad coverage of tyrosine and serine/threonine kinases.

The BioFocus Kinase Toolkitâ„¢ provides a two-dimensional map (2D Roadmap) of the key ligand-binding features within a customized ATP-site model, allowing predictions of affinity, selectivity, and likely off-target issues based on the compositions of the individual sub-sites. This knowledge can then be used to select the appropriate side chains or monomers with which to decorate the scaffolds.

DFG-Out Model

An approach to the design of kinase libraries with higher selectivity potential is to target the DFG-out allosteric pocket adjacent to the ATP site. BioFocus has developed a generalized binding model of the DFG-out pocket that enables the targeting of a range of inactive kinase conformations.

Binding Modes

click to enlarge

Figure 2. Ribbon diagram showing the binding of a potent SFK33 compound to the kinase PIM-1

A library design strategy focusing on alternative ligand-kinase binding modes is largely based on the novel binding modes observed in the cocrystal structure of a potent compound from a SoftFocus library (SFK33), bound to the kinase PIM-1 (Figure 2). In this case, the compound binds to a catalytic lysine residue whileÂ making no contact with the hinge region. This binding mode provides a unique paradigm for novel library design.

Only those scaffold ideas that pass this in silico docking are progressed to the next stage of evaluation, which includes a novelty check on structures and adherence to key hit/lead physicochemical property checks. Screening such libraries has generated information-rich data, generally consisting of higher hit rates (compared to screening diverse collections of unrelated compounds) together with key structure-activity relationship data that can speed up hit-to-lead programs.

Focusing on Success

By constantly refining the compounds using in silico methods, including those described above and with the development of innovative in silico models and applications such as Cresset BioMolecularâ€™s molecular Field technology, the latest advances in kinase research can be incorporated into novel libraries. Consequently, this may also provide a strong intellectual property position to those who screen them. Indeed, based on the screening of SoftFocus kinase libraries alone, over 70 known patents have been applied for or granted.

A recent example from Galapagos highlights this. Following a screen of some 16,000 BioFocus focused kinase compounds, three hit series were identified that showed structure-activity relationships against a novel rheumatoid arthritis target. Two of these compound series were progressed to the hit-to-lead phase and subsequently one series was optimized, and a compound is currently undergoing clinical trials. The project time from screening to preclinical candidate nomination was three years.

There is no doubt that the drug discovery process should be shortened whenever possible. It is essential to improve the lead discovery process. Focused compound libraries such as the SoftFocus collection have the inherent capabilities to provide a robust hit discovery process, with good hit-to-lead conversion rates and shorter development times.

Furthermore, such libraries can maximize the benefit of new techniques such as in silico modeling, enabling them to be consistently developed over time. BioFocus has also maintained flexibility in its library-generation processes using these techniques, which has enabled the development of novel libraries with proven results.

Source: genengnews.com

Posted under Compound Libraries, Compound Screening, Press Releases | Comments Off

DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening.

Last Updated on Monday, 11 January 2010 12:27 Written by Editor Monday, 11 January 2010 12:27

Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target.

Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats.

Results: Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their optimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database.

A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine.

Conclusions: DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations.

The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.

Author: David LagorceTania PenchevaBruno VilloutreixMaria Miteva
Credits/Source: BMC Chemical Biology 2009, 9:6

Posted under Cell Analysis, Cell-based Assays, Compound Screening, Discoveries, Innovations and Patents, Industry News, Press Releases | Comments Off

Lumpy Assay Results

Last Updated on Monday, 11 January 2010 12:23 Written by Editor Monday, 11 January 2010 12:23

When we screen zillions of compounds from our files against a new drug target, what can we expect? How many hits will we get, and what percentage of those are actually worth looking at in more detail?

These are long-running questions, but over the last twenty years some lessons have been learned. A new paper in J. Med. Chem. emphasizes one of the biggest ones: if at all possible, run your assays with some sort of detergent in them.

Why would you do a thing like that? Compound aggregation. The last few years have seen a rapidly growing appreciation of this problem. Many small molecules will, under some conditions, clump together in solution and make a new species that has little or nothing to do with their individual members. These new aggregates can bind to protein surfaces, mess up fluorescent readouts, cause the target protein to stick to their surfaces instead, and cause all kinds of trouble. Adding detergent to the assay system cuts this down a great deal, and any compound that’s a hit without detergent but loses activity with it should be viewed with strong suspicion.

The authors of this paper (from the NIH’s Chemical Genomics Center and Brian Shoichet’s lab at UCSF) were screening against the cysteine protease cruzain, a target for Chagas disease. They ran their whole library of compounds through under both detergent-free and detergent conditions and compared the results. In an earlier screening effort of this sort against beta-lactamase, nearly 95% of the hits (many of them rather weak) turned out to be aggregator compounds. This campaign showed similar numbers.

There were 15 times as many apparent hits in the detergent-free assay, for one thing. Some of these were apparently activating the enzyme, which is always a bit of an odd thing to explain, since inhibiting enzyme activity is a lot more likely. These activators almost completely disappeared under the detergent conditions, though. And even looking just at the inhibitors, 90% of the hit set in the detergent-free assay went away when detergent was added. (I should note that control cruzain inhibitors performed fine under both sets of assays, so it’s not like the detergent itself was messing with the enzyme to any significant degree).

They point out another benefit to the detergent assay – it seems to improve the data by keeping the enzyme from sticking to the walls of the plastic tubes. That’s a real problem which can kick your data around all over the place – I’ve encountered it myself, and heard a few horror stories over the years. But it’s not something that’s well appreciated outside of the people who set up assays for a living (and not always even among some of them).

So, let’s get rid of those nasty aggegators, right? Not so fast. It turns out that some of the compounds that showed this problem during the earlier beta-lactamase work didn’t cause a problem here, and vice versa. Even using different assays designed to detect aggregation alone gave varying results among sets of compounds. It appears that aggregation is quite sensitive to the specific assay conditions you’re using, so trying to assemble a blacklist of aggregators is probably not going to work. You have to check things every time.

One other interesting point from this paper (and the previous one): curators of large screening collections spend a lot of time weeding out reactive compounds. They don’t want things that will come in and react nonspecifically with labile groups on the target proteins, and that seems like a reasonable thing to do. But in these screens, the compounds with “hot” functional groups didn’t have a particularly high hit rate. You’d expect a cysteine protease to be especially sensitive to this sort of thing, with that reactive thiol right in the active site, but not so. This ties in with the work from Benjamin Cravatt’s group at Scripps, suggesting that even fairly reactive groups have a lot of constraints on them – they have to line up just right to form a covalent bond, and that just doesn’t happen that often.

So perhaps we’ve all been worrying too much about reactive compounds, and not enough about the innocent-looking ones that clump up while we’re not looking. Detergent is your friend!

Source: corante.com

Posted under Cell Analysis, Cell-based Assays, Compound Screening, Industry News, Press Releases | Comments Off

Syntopix edges closer to early revenue streams, announces positive phase II cosmetic study of antimicrobial compound

Last Updated on Saturday, 24 July 2010 04:09 Written by Editor Monday, 11 January 2010 11:32

Specialty antimicrobial research and development company Syntopix (AIM: SYN) took another step closer to commercialising a new product targeting a large consumer healthcare market, reporting good results from the trials of its new compound for the treatment of acneic skin, a condition that affects 85% of the population during their lifetime.

Over the course of the trials, formulations using the Syntopix dermatological compound SYN0126 alone or in combination with the lipid-targeted antioxidant SYN0854, outperformed a marketed cosmetic product containing 2% salicylic acid, producing a 30% mean reduction in total spot count over an eight week period.

The reduction in non-inflamed spots for both of the Syntopix formulations approached the efficacy seen with a number of topical prescription treatments. In contrast, the negative control group managed a mean reduction in non-inflamed spots of just 9.8% whilst the group using the marketed product (positive control) recorded a 7.8% mean increase.

The company believes the positive study results have put it closer to commercialising the product with discussions with potential clients already in place.

â€œThis study confirms that our rigorous screening programme is yielding results.Â Â We areÂ now actively pursuing discussions with leading cosmetic and consumer healthcare companies to investigate the possibility of securing a licensing agreementÂ forÂ SYN0126Â andÂ are confident that the positive results from this study will lead to commercial deals in the near future,â€ said chief executive of Syntopix, Stephen Jones.

A further Phase II cosmetic study is set to take place in the second half of 2010.

Syntopix simultaneously released a business update, announcing its intention to focus on its three most advances compounds, SYN0126, SYN1113 and SYN0017 to accelerate their commercialisation, while continuing its screening programme to identify antimicrobial compounds for use in over-the-counter (OTC) and cosmetic products, particularly those used in skin care, oral care and chewing gum.

The company added that it continued to develop a strong working relationship with Procter & Gamble (NYSE: PG) and was in close collaboration to develop antimicrobials for use in an undisclosed â€œmajor consumer healthcare brandâ€ and that it has renewed its exclusivity and evaluation agreement with another â€œmajor consumer healthcare company,â€ announced back in April. Syntopix has also secured its tenth UK patent to protect the SYN0126 compound.

Posted under Business and Investment, Collaborations, Press Releases | Comments Off

GSK Signs On Astex in Broad Partnership for About $33M Up Front

Last Updated on Saturday, 24 July 2010 04:09 Written by Editor Monday, 11 January 2010 11:30

GlaxoSmithKline (GSK) has inked a deal with Astex Therapeutics to discover, develop, and commercialize compounds directed against multiple targets for Â£20 million (about $33 million) up front. Astex is eligible to development and regulatory milestones of over Â£300 million (roughly $496.47 million) if all programs are successfully developed and commercialized.

The up-front payment comprises Â£12.5 million (approximately $20.68 million) in cash and Â£7.5 million (about $12.41 million) in equity. Milestones include fees related to nonclinical success totaling more than Â£37 million (roughly $61.23 million). Additionally, Astex is entitled to tiered royalties on each program.

Astex will apply its fragment chemistry platform, Pyramidâ„¢, to various targets of interest to GSK. The firms will form joint program teams to identify candidate compounds. Astex will be primarily responsible for initial fragment screening and lead discovery. GSK will primarily be responsible for optimization of the identified lead compounds. Additionally, GSK will be solely responsible for completing preclinical and clinical development of all products arising from the collaboration and for their commercialization globally.