Archive for the ‘Industry News’ Category
InVivo and CEVEC pharmaceuticals sign license agreement regarding the use of human CAP-Tâ„¢ Technology for production of recombinant proteins
Last Updated on Thursday, 8 October 2009 10:44 Written by Editor Thursday, 8 October 2009 10:44
Cologne, Germany, October 01, 2009 / b3c newswire / – CEVEC Pharmaceuticals, the developer of a novel human expression system derived from amniocytes and the contract manufacturer InVivo BioTech Services GmbH announced today the signing of a strategic license agreement. This license enables InVivo to offer its customers the production of their diagnostic ad preclinical grade material very fast and in highest quality, including authentic human glycosylation patterns, using the novel and proprietary CAP-Tâ„¢ transient expression system.
CAP-T™ Technology is based on CAP® cells, the stable cell line from CEVEC. The non-tumor origin cells have high expression rates of human proteins and grow in serum-free suspension culture and post-translational modifications are human-like. Process times are reduced by means of large-scale transient transfection.
“After launching our new transient cell in the US market we are delighted to have now our first customers in Europe not only using our stable expression system but also working with our new transiently expressing human cell line. With expression rates outperforming any other human system on the market, e.g. HEK 293 freestyle and others, while offering highest quality human like proteins, we offer our customers a unique state of the art cell line,â€Â Wolfgang Kintzel, CCO of CEVEC Pharmaceuticals GmbH states.
Rainer Lichtenberger, CEO of CEVEC, adds. “Because posttranslational modifications play a significant role for the bioactivity of recombinant proteins it is of crucial importance to produce proteins with human-like glycosylation and sialylation. With our proprietary human cell lines, CAP for permanent producer cells for proteins and the novel CAP-T system, only CEVEC is able to offer a unique range of versatile human cell expression systems to our customers, from early discovery to protein manufacture. This license agreement contributes significantly to CEVECs goal becoming the leading cell line supplier for protein production with human cell expression systems.â€
Link to the news release
About CEVEC Pharmaceuticals GmbH – www.cevec-pharmaceuticals.com
CEVEC Pharmaceuticals GmbH, operational since 2004 was founded by a group of internationally renowned scientists and clinicians from the University of Cologne, Germany. Based on their experience and theirlongstanding collaborative work they had experienced a lack of innovative expression systems formore efficient production of biologics such as recombinant proteins or gene therapy vectors. CEVEC’s novel proprietary human CAP® and CAP-T™ expression systems are ideal for manufacturing complex biopharmaceutical molecules with human glycosylation patterns.
About InVivo BioTech Services GmbH – www.invivo.de
InVivo is a contract manufacturing organization (CMO) dedicated to the development and production of monoclonal antibodies and expression of recombinant proteins. Based in Hennigsdorf, Germany, just outside Berlin, InVivo is an ISO 9001 certified company with over ten years experience in mammalian cell culture and protein production. More than 1100 different hybridomas have been cultivated in InVivo’s proprietary serum-free media ISF1 for high productivity and cost benefits in cultivation and purification. Furthermore InVivo offers the complete range of modern protein expression techniques. Starting from synthetic or amplified cDNA your protein can be stable expressed in bacteria, insect and mammalian cell lines or alternatively transient expressed.
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Baylor researchers find fat cell blocker
Last Updated on Tuesday, 8 September 2009 10:09 Written by Editor Tuesday, 8 September 2009 10:09
A small molecule that turns off the genes responsible for making fat cells has been discovered by a team of Baylor College of Medicine and Japanese researchers.
Dubbed “fatostatin,†the molecule blocks a protein in the cell that starts the cascade of events that turns on the 63 genes in the nucleus responsible for the generation of fat cells, said Salih Wakil, professor of biochemistry and molecular biology at BCM.
The report appears in the journal Chemistry and Biology.
“That is the exciting thing,†said Wakil. “This goes to the most basic level of the expression of genes that cause fat.â€
When mice with a predisposition to be obese received fatostatin, they lost weight, their cholesterol and fatty acid synthesis decreased. They had less resistance of insulin (a factor in diabetes), and their livers, which were pale because of fat buildup, returned to normal.
Drugs that lower cholesterol already exist, but they block only a single enzyme in the fat-generating pathway. Fatostatin stops the process at the beginning, said Wakil.
Wakil said one of his colleagues, Motonari Uesugi, now of Kyoto University in Japan, discovered the compound by screening a library of an estimated 10,000 compounds.
Lutfi Abu-Elheiga, associate professor of biochemistry and molecular biology at BCM was also a major contributor.
Source: bizjournals.com
Posted under Compound Libraries, Discoveries, Innovations and Patents, Industry News, Press Releases | Comments Off
Vanderbilt Joins National Consortium to Develop New Cancer Therapies
Last Updated on Tuesday, 25 August 2009 03:27 Written by Editor Tuesday, 25 August 2009 03:27
Vanderbilt University has been selected as one of 10 centers in the nation to participate in the Chemical Biology Consortium (CBC), a major new initiative to facilitate the discovery and development of new agents to treat cancer.
As one of four Chemical Diversity Centers, Vanderbilt’s role in the consortium will be to synthesize and optimize new compounds as potential cancer therapeutics.
“This is a real tribute to our growth in cancer chemistry and the leverage between the Vanderbilt Institute of Chemical Biology (VICB) and the Vanderbilt-Ingram Cancer Center (VICC),†said Lawrence Marnett, Ph.D., the Mary Geddes Stahlman Professor of Cancer Research and director of the VICB.
Alex Waterson, Ph.D., research assistant professor of Pharmacology and director of the VICB’s Chemical Synthesis Core, will lead efforts developing small molecule drug candidates. Gary Sulikowski, Ph.D., Stevenson Professor of Chemistry and a co-director of the core, will direct projects involving natural products.
Designed to accelerate the discovery and development of effective, first-in-class targeted therapies, the CBC will choose high-risk targets that are of low interest to the pharmaceutical industry. The CBC is a National Cancer Institute initiative administered by contractor SAIC-Frederick, Inc.
“It’s exciting in the sense that, right off the bat, (the NCI) said that the goal of this program is to develop drugs for cancer treatment,†said Sulikowski. “They’re looking for unique targets, unique approaches, and they think that academia may offer that.â€
“Oftentimes pharmaceutical companies will not go after targets that are not expected to be huge blockbusters,†said Waterson, who came to Vanderbilt in 2008 from GlaxoSmithKline where he had worked for seven years on oncology drug development projects. “So an effort like this can fill in a niche that industry is not taking on at the moment.â€
One particular area of interest is in screening and developing natural products as potential drug candidates.
This “is something that pharmaceutical industry has de-emphasized just because of the way things have evolved,†said Sulikowski. “And that’s one of our advantages, in that we have expertise in natural products as well as medicinal chemistry.â€
Cancer drug development poses many challenges – but also unique opportunities.
“There is a difficulty in that cancer is not a single disease; it’s a family of loosely related diseases,†said Waterson. “There’s an opportunity for a whole myriad of different treatments that are pretty much only tailored to a small subset of people, where your treatment addresses their specific need.â€
A unique aspect of the CBC is the NCI’s efforts to establish intellectual property rights for investigators and institutions that develop assays or drug candidates.
“The hope is that by recognizing establishment of intellectual property as one of the goals, they will attract people with the best ideas, things that really might be able to become a drug,†said Waterson.
Vanderbilt’s involvement with the CBC, along with the recent arrival of Stephen Fesik, Ph.D., who previously led cancer drug discovery efforts at Abbott Laboratories, will make Vanderbilt “one of the best academic institutions doing cancer drug discovery in the country,†Marnett said.
Other Vanderbilt investigators involved in this effort include:
• Brian Bachmann, Ph.D., assistant professor of Chemistry and Biochemistry
• Jeffrey Johnston, Ph.D., professor of Chemistry
• Jens Meiler, Ph.D., assistant professor of Chemistry, Pharmacology and Biomedical Informatics
• Craig Lindsley, Ph.D., associate professor of Pharmacology and Chemistry, and director of Medicinal Chemistry
Other sites participating in the CBC are:
• The Burnham Institute for Medical Research, in La Jolla, Calif.;
• Southern Research Institute in Birmingham, Ala.;
• University of North Carolina at Chapel Hill;
• Georgetown University in Washington, D.C.;
• University of Minnesota;
• University of Pittsburgh;
• University of Pittsburgh, Drug Discovery Institute;
• University of California, San Francisco;
• SRI International in Menlo Park, Calif.; and
• Emory University in Atlanta
This project has been funded in whole or in part with Federal Funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Source:Â vanderbilt.edu
Posted under Cancer Research, Grants and Awards, Industry News, Press Releases, Research Projects | Comments Off
Killing Cancer Stem Cells
Last Updated on Tuesday, 25 August 2009 02:36 Written by Editor Tuesday, 25 August 2009 02:36
Recent evidence suggests that certain cancers may persist or recur after treatment because a small population of cells, called cancer stem cells, remains behind to seed new tumors. Though scientists are not yet certain about the role cancer stem cells play in disease, evidence is accumulating that these cells are particularly resistant to chemotherapy and radiation, and can linger in the body even after treatment.Several research groups have begun looking for substances that kill these cells. A new approach, developed by researchers at the Whitehead Institute for Biomedical Research and the Broad Institute of MIT and Harvard, makes use of high-throughput screening methods to identify chemicals that selectively target these elusive cells. In a study published today in Cell, the researchers identify one particular drug that kills breast cancer stem cells in mice. Although it is still unclear whether the drug will be useful in humans, the researchers believe their study demonstrates that it’s possible to target these cells selectively.
Because cancer stem cells, which have the ability to give rise to new tumors, may remain behind after chemotherapy and radiation treatments, finding ways to target these cells specifically may offer a way to make treatment more effective. But accessing and studying cancer stem cells has been challenging because very few are present in tumors and they are difficult to generate and maintain outside the body. Other groups have recently screened for drugs that target leukemia stem cells and brain cancer stem cells. In the Cell paper, a team led by the labs of Eric Lander at the Broad Institute and Robert Weinberg at the Whitehead Institute developed a way to generate a large number of cells that mimic naturally occurring epithelial cancer stem cells; these cells can be maintained in this state for long periods of time.
Epithelial cancers are the most common types of cancer in adults and affect the skin and inner lining of organs in the body. Using epithelial breast cancer cells, the researchers introduced a genetic change in these cells, causing them to take on the properties of mesenchymal cells, which form connective tissue in the body. Piyush Gupta, a co-author at the Broad Institute, says that for reasons not completely known, when this “epithelial-to-mesenchymal transition†is performed on breast cancer cells, it promotes the development of a large number of cells that he says are “indistinguishable from cancer stem cells.†These cells can then be grown in tiny pockets on plates and screened robotically for their response to large collections of chemicals.
The researchers used a library of 16,000 chemicals at the Broad Institute to look for compounds that killed these transformed breast cancer stem cells more effectively than they killed normal breast cancer cells. Gupta explains that since cancer stem cells are usually resistant to drugs, relatively few chemicals are effective–a mere 32 compounds were identified in the screen as preferentially treating breast cancer stem cells.
After some initial testing of several compounds, the researchers focused on one drug called salinomycin. They compared it to the actions of a drug commonly given in breast cancer chemotherapy, paclitaxel (also known by its brand name, Taxol), in cultured cells and in mice. While paclitaxel treatment leads to a higher proportion of drug-resistant cancer stem cells, salinomycin had the opposite effect, reducing the number of breast cancer stem cells in cultured cells more than 100 times more effectively than paclitaxel. The drug also reduced breast tumor growth in mice, although the reduction was less dramatic.
Gupta says that it’s not clear whether salinomycin will be a clinically useful drug, because it has not yet been tested in humans. The team is continuing to study this initial candidate drug, but he also notes, “we’re following up on several others that we think may be promising.â€
Jeffrey Rosen, a breast cancer researcher at Baylor College of Medicine, in Houston, TX, says that the study is an early example of a promising new turn in the hunt for cancer therapies. “It’s very exciting that some groups are starting not to view tumors as homogeneous entities but to target subpopulations of cells we think are import for drug resistance,†he says. However, Rosen notes that the results in mice were not as promising as the drug’s performance in cells. He says that the cancer field is hampered by a lack of good animal models to determine which drugs will be relevant for therapies. The problem, he says, is “once you pull out a compound or drug, then how do you actually go the next step and show that it’s really going to work?â€
Weinberg calls the study “the first step in the direction of trying to eliminate these cells in tumors.†He believes that even if the role of cancer stem cells in different kinds of cancer has not been resolved, “we have no doubt that getting rid of them is going to be an important part of creating cures.â€
Although this study focused on breast cancer, the researchers anticipate that the screen could be applied to any kind of epithelial cancer. Gupta says that while targeting cancer stem cells may not necessarily be a “magic bullet†in cancer treatment, “if you have a certain subpopulation of cancer cells that are resistant to standard treatment, you would want to find a compound that targets these cells.†He adds that a drug that targets cancer stem cells could be used in combination with standard treatments to ensure that resistant cells are not left behind.
Source: technologyreview.com
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National Cancer Institute names Emory to nationwide NCI chemical biology consortium
Last Updated on Tuesday, 25 August 2009 02:27 Written by Editor Tuesday, 25 August 2009 02:27
CBC will support rapid development of innovative, targeted cancer therapies
Emory University’s Chemical Biology Discovery Center has been selected by SAIC-Frederick, Inc. (SAIC-F) to be part of an 11-member national consortium aimed at accelerating the discovery and development of new and innovative, targeted cancer therapies. SAIC-F is the prime contractor to the National Cancer Institute at Frederick (NCI-Frederick).
The national Chemical Biology Consortium (CBC) will bridge the gap between basic scientific investigation and clinical research supported by the NCI. The consortium will focus on unmet medical needs, such as drugs that are of low interest to the pharmaceutical industry but that could have significant benefit for patients. It is expected to bring the skills of hundreds of chemical biologists, oncologists, and synthetic and medicinal chemists to bear on particularly challenging problems in molecular oncology.
Examples of the CBC’s innovative discovery pathways could include re-engineering investigators’ assays into high-throughput screens; rapidly synthesizing natural products that show promise as drug targets in a particular form of cancer; making new compounds water-soluble; and accelerating the development of drug candidates with great clinical promise.
As one of three Specialized Application Centers in the NCI Consortium, the Emory Chemical Biology Discovery Center will focus its broad capability and special expertise on protein-protein interactions in cancer through assay development and implementation, high-throughput screening, medicinal chemistry optimization and informatics, with the participation of an intellectual property specialist.
“Recent advances in our understanding of the molecular basis of cancer have led scientists to identify oncogenes and pathways involved in tumor development that offer unprecedented opportunities for innovative drug discovery,” says Haian Fu, PhD, director of the Emory Chemical Biology Discovery Center and principal investigator of the Emory CBC center. Fu is professor of pharmacology, hematology & medical oncology in Emory University School of Medicine and a co-leader of the Discovery and Developmental Therapeutics Program of the Emory Winship Cancer Institute.
“This consortium will allow the NCI and the consortium members to pursue innovative strategies and dedicate resources to interrogating new signaling pathways and promising but difficult targets for the rapid discovery and development of clinically viable new compounds that might not otherwise be developed. Examples include pediatric cancer targets,” says Fu.
The Emory center is anchored by investigators within the Emory Winship Cancer Institute and integrated with drug discovery and development capabilities of researchers throughout campus. Co-principal investigators of the Emory CBC Center are Fadlo Khuri, MD, deputy director for clinical and translational research in Emory Winship Cancer Institute and professor and chair of hematology & medical oncology, and Dennis Liotta, PhD, Emory professor of chemistry.
“Emory has a strong foundation of team science and collaboration, high throughput screening expertise and a solid record of success in the NIH Molecular Libraries Screening Centers Network,” says Liotta. “We have a team of assay biologists, screening scientists and informatics experts working side by side with medicinal chemists. Our record of drug discovery and partnerships with pharmaceutical companies show that we have the experience and expertise to serve as national leaders in cancer drug discovery.”
The Georgia Cancer Coalition (GCC) is providing matching funds for the Emory CBC Center of approximately $750,000. Emory will provide other matching funds for the Center. The Georgia Research Alliance provided initial support for the Chemical Biology Discovery Center.
“We are proud and delighted that the National Cancer Institute has once again reached out to Georgia for leadership in cancer control,” says William J. Todd, president and chief executive officer of the Georgia Cancer Coalition. “By supporting Emory’s participation in this national cancer drug discovery initiative, we are reinforcing the state’s comprehensive cancer control plan goal to accelerate improvements in cancer treatment. This designation brings us yet one step closer to making Georgia one of the nation’s premier states for cancer control.”
“As a molecular oncologist and a cancer clinician, I am very pleased with this opportunity for Emory’s involvement in a national NCI consortium to speed drug discovery,” says Khuri. “This is a very exciting time for cancer research, and I am optimistic this consortium will result in significant research advances that soon will benefit patients with particularly challenging types of cancer.”
As a member of the national consortium, the Emory center will join forces with the NCI and other national centers for project-team based accelerated cancer drug discovery operations from target identification, high throughput screening, all the way through clinical trials. It will be funded through a contractual agreement mechanism with the NCI.
In 2005 the National Institutes of Health (NIH) awarded Emory $9 million in the pilot phase of the National Molecular Libraries Screening Center Network (MLSCN). The network uses high-tech screening methods on huge libraries of small molecular compounds to identify probes as promising molecular research tools.
Emory’s CBC selection by the NCI built on Emory’s already established Chemical Biology Discovery Center and its experience in MLSCN. The Emory Chemical Biology Discovery Center is an interdisciplinary collaboration among research departments in Emory School of Medicine and Emory College. The Center also uses high-throughput technologies to screen libraries of hundreds of thousands of small molecule compounds against promising molecular targets identified by Emory scientists.
For more information about the NCI Chemical Biology Consortium: http://plan,cancer.gov./Chemical_Biology_Consortium.htm
For more information about the Emory Chemical Biology Discovery Center: http://www.emory.edu/chemical-biology/#
Emory Medicine Magazine article on drug discovery at Emory: http://whsc.emory.edu/_pubs/em/2006spring/drug_discovery.html
NIH Names Emory University a National Molecular Libraries Screening Center (press release) http://whsc.emory.edu/press_releses_print.cfm?announcement_id_seq=4040
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Forma Therapeutics, Novartis team on cancer drugs
Last Updated on Tuesday, 25 August 2009 10:31 Written by Editor Tuesday, 25 August 2009 10:31
Forma Therapeutics Inc. said that it has entered into a collaboration agreement with Novartis AG to use Forma’s cell-based screening platform to discover inhibitors for undisclosed protein-protein interaction targets to help develop cancer drugs.
No financial terms of the deal were disclosed. The funding arm of pharmaceutical giant Novartis, the Novartis Option Fund, was one of the investors in Cambridge-based Forma’s $4 million funding round in March of 2008.
Earlier this month, Forma and The Leukemia & Lymphoma Society partnered in an effort to move the health agency’s research products toward development quickly. As part of the deal, Forma will help design ten small molecule drugs using its Computational Solvent Mapping technology.
In March, Forma reported it would collaborate with the Experimental Therapeutics Centre (ETC) of Singapore on development of new anti-cancer drugs. The intent is to use Forma’s transformative chemistry platform to discover new compounds that ETC will develop.
Forma Therapeutics relies on an integrated transformative biology and chemistry-based approach to develop its drugs. It uses a cell-based screening platform to permit the screening of discrete targets in cells. Headquartered in Cambridge, Forma has research operations in Connecticut, Singapore and Beijing.
Posted under Business and Investment, Cancer Research, Compound Screening, Discoveries, Innovations and Patents, Drug Development, Industry News, Press Releases | Comments Off
SRI announces selection by the National Cancer Institute as a Chemical Biology Consortium center
Last Updated on Friday, 21 August 2009 02:19 Written by Editor Friday, 21 August 2009 02:19
Menlo Park, Calif.—July 22 , 2009—SRI International, an independent nonprofit research and development organization, announced today that SRI’s Center for Cancer Research was selected by the National Cancer Institute (NCI) for a leading role in the newly-formed “Chemical Biology Consortium” (CBC), a collaborative drug discovery partnership focused on advancing new cancer therapeutics active against novel molecular and genetic cancer targets. Based on its track record of cancer drug discovery and development, SRI was chosen to lead three of the CBC’s research and development centers: Comprehensive Chemical Biology Screening, Chemical Diversity, and Specialized Applications.
SRI has decades of experience in successfully identifying, developing and advancing novel compounds into clinical evaluation. SRI’s Center for Cancer Research, comprised of biologists and medicinal chemists with expertise in fundamental and applied cancer research, focuses on the study of tumor microenvironment, tumor metabolism, and aberrant signaling pathways that cause cancer. Through collaborative partnerships, SRI’s Center for Cancer Research has been successful in generating an extensive drug pipeline translating discoveries into beneficial treatments. SRI’s drug discovery process, guided by a combination of biological screens and computational methods, will be a key component of the NCI Chemical Biology Consortium program.
“SRI is proud to be selected to join this innovative NCI program and to continue our long-standing support of NCI’s mission to discover, develop, and bring new drugs to cancer patients,” said Lidia Sambucetti, Ph.D., senior director of SRI’s Center for Cancer Research. “Our multidisciplinary research team will bring proven expertise in fundamental and applied cancer research, backed by SRI’s fully-integrated preclinical capabilities.”
The goal of the Chemical Biology Consortium is to discover and develop new cancer therapeutics, particularly those that are beyond the scope of standard biopharmaceutical practice. The CBC will focus on therapeutic opportunities in high-risk, under-represented areas to advance the discovery of compounds active against novel molecular and genetic cancer targets.
Sambucetti will serve as the overall principal investigator of SRI’s CBC program and the Comprehensive Chemical Biology Screening Center. She will collaborate with Mary Tanga, Ph.D., an SRI senior director of medicinal chemistry, who will lead the Chemical Diversity Center, and Keith Laderoute, Ph.D., an SRI distinguished scientist, who will lead the Specialized Applications Center.
As the principal investigator of the Comprehensive Chemical Biology Screening Center, Sambucetti was invited to join the CBC Steering Committee, an NCI advisory panel that will work to ensure that CBC Centers are efficiently bridging the gap between basic scientific findings and NCI-supported clinical research.
To optimize high-quality leads and accelerate the drug discovery process, SRI will be working with BioComputing Group, Inc., a developer of computational screening, hit-to-lead, and lead optimization tools with particular emphasis on structure-guided drug discovery. These tools employ novel molecular descriptors that are derived from active compounds within the target family and from the structure of the target protein that can be applied to the evaluation of compounds from a library as well as compounds not yet synthesized. BioComputing Group, Inc. (www.BioPredict.com) has a significant track record of success in applying its tools in a hypothesis-driven paradigm to accelerate drug discovery efforts of its collaborators and clients, having placed multiple compounds into clinic with significantly reduced numbers of compounds screened and synthesized and with significantly shortened time frames.
This project has been funded in whole or in part with Federal Funds from the National Cancer Institute, National Institutes of Health, under Contract No. N01-C0-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.
About SRI’s Biosciences Division
SRI International’s Biosciences Division teams with pharmaceutical and biotechnology companies, academia, foundations, and government agencies to solve important problems in global health. SRI Biosciences conducts basic research, drug discovery, and drug development, including contract research. SRI has all of the resources necessary to take R&D programs from “idea to IND”™—from initial discovery to investigational new drug applications to start human clinical trials—and specializes in cancer, immunology and inflammation, infectious disease, and neuroscience research. SRI’s internal drug pipeline has yielded several marketed drugs, several additional drugs currently in clinical trials, and more than a dozen programs in preclinical development or early discovery. In its CRO business, SRI has helped advance more than 100 drugs into clinical trials, several of which have reached the market. SRI is also working at the nexus of science and technology to create new technology platforms for the next generation of drug discovery and development in areas such as diagnostics, drug delivery, medical devices, and systems biology.
About SRI International
Silicon Valley-based SRI International is one of the world’s leading independent research and technology development organizations. SRI, which was founded by Stanford University as Stanford Research Institute in 1946 and became independent in 1970, has been meeting the strategic needs of clients and partners for more than 60 years. Perhaps best known for its invention of the computer mouse and interactive computing, SRI has also been responsible for major advances in networking and communications, robotics, drug discovery and development, advanced materials, atmospheric research, education research, economic development, national security, and more. The nonprofit institute performs sponsored research and development for government agencies, businesses, and foundations. SRI also licenses its technologies, forms strategic alliances, and creates spin-off companies. In 2008, SRI’s consolidated revenues, including its wholly owned for-profit subsidiary, Sarnoff Corporation, were approximately $490 million.
Source: www.sri.com
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Cognition Therapeutics Closes Series A Financing to Advance Drug Candidates for Alzheimer’s Disease
Last Updated on Friday, 21 August 2009 01:12 Written by Editor Friday, 21 August 2009 01:12
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Start-up company continues momentum with selection of disease-modifying small molecule drug leads for behavioral testing
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PITTSBURGH, July 16 /PRNewswire/ — Cognition Therapeutics Inc., a Pittsburgh-based drug discovery company developing small molecule disease-modifying treatments for Alzheimer’s, has closed on a $1.21M Series A financing. The round was led by Ogden CAP, LLC of New York City and includes M5Invest Partners of Villanova, PA, the Pittsburgh Life Sciences Greenhouse, Innovation Works (Pittsburgh), and several individual investors. The round included both new investments and the conversion of existing convertible notes.
“This investment facilitates the advancement of our existing lead molecules towards a major milestone,” said Cognition Therapeutics President and CEO Hank Safferstein, Ph.D., J.D. “Our combination of novel, small molecule drug candidates and biologically-relevant screening methods is unique in the pharmaceutical industry. We’re pleased to have Ogden CAP and M5Invest join our other investors in supporting our pioneering approach to treat or prevent Alzheimer’s disease by targeting the proteins that cause the earliest stages of this disease”. “As early investors, we are impressed by Cognition Therapeutics’ combination of cutting-edge technology, influential and experienced leadership, and large clinical and commercial potential,” said Robert Gailus, senior advisor to Ogden CAP. “Alzheimer’s disease is a major health epidemic that places increasing strains on the world’s healthcare systems as the population ages. The drug candidates being developed by Cognition have the potential to significantly impact this devastating disease,” Gailus continued. Alzheimer’s disease affects an estimated four and a half million people in the United States today. That number is expected to exceed 12 million people by 2050. Funds raised in this round will support advancement of Cognition Therapeutics’ pioneering lead molecules that block the activity of the toxic oligomeric form of Abeta protein that interferes with normal learning and memory. Studies from the world’s leading academic laboratories indicate that the memory deficits caused by the oligomeric protein are among the earliest changes seen in Alzheimer’s disease and Mild Cognitive Impairment, the precursor to Alzheimer’s. These studies indicate that blocking the effects of this protein may halt or reverse Alzheimer’s disease. Cognition will use these funds to test its most promising lead molecules in behavioral models of Alzheimer’s disease. “The advancement of the company’s lead compounds into behavioral testing represents a significant milestone for the company,” says Dr. Franz Hefti, Chairman of the Board. “Cognition’s scientific approach is unique among the approaches being taken by the pharmaceutical industry today. Cognition has a novel Alzheimer’s disease model for the critical molecular step that causes memory loss. In addition, the company’s proprietary chemistry is based on natural molecular scaffolds which brought us effective drugs like aspirin, lidocaine and taxol. We anticipate new disease-modifying drugs for Alzheimer’s disease will result from this unique combination,” Dr. Hefti continued. About Cognition Cognition Therapeutics, Inc. is a leader in the discovery and development of small molecule therapeutics targeting the toxic proteins that cause the cognitive decline associated with Alzheimer’s disease and other degenerative diseases of the human brain. Toxic proteins play a crucial role in a large class of diseases, and there are currently no therapeutics available to prevent or block the destructive effects of toxic oligomeric proteins. Cognition has leveraged its scientific expertise with these difficult targets to pioneer the use of proprietary assays that emphasize functional responses and proprietary medicinal chemistry that ensures novel, high quality small-molecule drug candidates for the treatment of these diseases. Cognition has developed a number of screening strategies to identify small molecules capable of blocking the central toxicity of proteins in Alzheimer’s disease and other neurodegenerative diseases. These assays emphasize phenotypic or functional responses of mature primary neurons to the toxic proteins. Cognition’s proprietary chemistry platform converts natural products into low molecular weight chemically stable druglike molecules, and is thus a source of novel pharmacophores and valuable drug candidates. These two technology platforms harken back to the origins of the pharmaceutical industry, when phenotypic responses were the sole screening method and natural product derivatives formed the starting materials for successful drug discovery. Cognition Therapeutics was founded on small molecule chemical libraries licensed from co-founder Dr. Gilbert Rishton at California State University Channel Islands and proprietary screening strategies established by co-founder and Chief Science Officer Dr. Susan Catalano. After initial investment and relocation to Pittsburgh, the company secured Dr. Hank Safferstein as President and CEO, bringing with him more than 15 years of leadership experience in drug development, commercialization and marketing for a number of public and private companies. www.cogrx.com. About Ogden CAP, LLC Ogden CAP, LLC is a New York company that has investments is a wide variety of asset classes, including venture capital. Over the past two years Ogden CAP, LLC has invested in 10 early stage companies. Besides its investment in Cognition, Ogden CAP, LLC has two other investments in the Pittsburgh area: FASTTAC, a document control and management company for the construction industry, and TSG, Inc. an energy company that converts coal to fuels. About the Pittsburgh Life Sciences Greenhouse (PLSG) The Pittsburgh Life Sciences Greenhouse (PLSG) provides capital investments and customized company formation and business growth services to western Pennsylvania’s life sciences enterprises. The PLSG supports biosciences companies with promising innovations in the following concentrations: Biotechnology Tools, Diagnostics, Healthcare IT, Medical Devices and Therapeutics. The PLSG is propelling the sustainable growth of the region’s life sciences economy by accelerating research and technology commercialization with seed and early-stage companies; connecting investors with their Investment Portfolio companies; expanding established life sciences ventures and relocating biomedical companies to Pennsylvania. About Innovation Works (IW) Innovation Works provides risk capital and business expertise to the most promising early-stage technology companies in Southwestern PA to help them grow and succeed. Innovation Works is one of the most active seed-stage investors in the country, having invested in more than 120 emerging technology companies since beginning their seed fund in 1999. Those companies have gone on to raise over $600 million in additional capital from a diverse set of VCs, private investors, strategic partners and other sources of capital. |
SOURCE Cognition Therapeutics Inc.
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Horizon Discovery signs screening agreement with SuperGen Inc.
Last Updated on Friday, 21 August 2009 01:04 Written by Editor Friday, 21 August 2009 01:04
Horizon’s X-MAN (Mutant And Normal) cell-line technology provides the first genetically-defined and patient-relevant in vitro models of human cancer. These models are being used by a growing number of Pharma and Biotech companies to rationalize key steps of the ‘targeted’ drug development process, and thus accelerate and economize the burgeoning field of ‘personalised’ medicine.
The agreement covers the screening of a number of lead compounds on a wide panel of human isogenic cell-lines comprising target genotypes of interest to SuperGen. The approach may enable SuperGen to gather information relating to the selectivity and mode-of-action of their compounds using model in-vitro systems.
“Dr Darrin M Disley, Commercial Director and Chairman of Horizon says “working with SuperGen is an exciting development for Horizon. In this expandable agreement, we hope to further prove the potential of our human X-MAN models in a screening environment; thus facilitating a long and productive relationship with SuperGen.â€
SuperGen will pay Horizon undisclosed fees during the term of the agreement. Work between the parties will begin in July 2009.
About Horizon Discovery
Horizon Discovery is a translational genomics company founded in June 2007 and is headquartered at the Babraham Research Campus, Cambridge, UK and with additional research laboratories in Torino, Italy. Horizon’s goal is to convert new information on the genetic causes of cancer into laboratory models that will facilitate the discovery of drugs that target these defects. Central to this aim is Horizon Discovery’s offering of X-MAN cell-lines, which represent accurate models of defined cancer patient populations and their matched normal genetic backgrounds – a missing link in the rational and efficient development of novel targeted anti-cancer agents.
Source: Cambridge Network
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The Further In You Go, The Bigger It Gets
Last Updated on Friday, 21 August 2009 01:02 Written by Editor Friday, 21 August 2009 01:02
I had a printout of the structure of maitotoxin on my desk the other day, mostly as a joke to alarm anyone who came into my office. “Yep, here’s the best hit from the latest screen. . .I hear that you’re on the list to run the chemistry end. . .what’s that you say?”
This is, needless to say, one of the largest and scariest marine natural product structures ever determined (and that determination has been no stroll past the dessert table, either).
But that’ hasn’t stopped people from messing around with it. And there’s much speculation that other people are strongly considering messing around with it, too – you synthetic chemists can guess the sorts of people that this might be, and their names, and what it might be like to sit through the seminars that result, and so on.
I fear that a total synthesis of maitotoxin would be largely a waste of time, but I’m willing to hear arguments against that position. Just looking at it, though, inspires thought. This eldrich beastie has 98 chiral centers. So let’s do some math. If you’re interested in the SAR of such molecules, you have your choice of (two to the 98th) possible isomers, which comes out to a bit over (3 times ten to the 29th) compounds. This is. . .a pretty large number. If you’re looking for 10mg of each isomer to add to your screening collection (no sense in going back and making them again), then you’re looking at a good bit over half the mass of the entire Earth. And that’s just in sheer compounds; we’re not counting the weight of vials, which will, I’d say, safely move you up toward the planetary weight of a low-end gas giant. We will ignore shelving considerations in the interest of time.
Recall that yesterday’s post gave a number of about 27 million compounds below 11 heavy atoms. You could toss 27 million compounds into a collection of ten to the 29th and never see them again, of course. But that brings up two points: one, that the small-compound estimate ignores stereochemistry, and we’ve been getting those insane maitotoxin numbers by considering nothing but. The thing is, with only 11 non-hydrogen atoms, there aren’t quite as many chances for things to get out of control. The GDB compound set goes up only to 110 million or so if you consider stereoisomers, which actually isn’t nearly as much as I’d thought.
But the second point is that this shows you why the Berne group stopped at 11 heavy atoms, because the problem becomes intractable really fast as you go higher. It’s worth remembering that the GDB people actually threw out over 98% of their scaffolds because they represented potential ring structures that are too strained to be very stable. And they only considered C, N, O and F as heavy atoms (even adding sulfur was considered too much to deal with, computationally). Then they tossed out another 98 or 99% of the structures that emerged from that enumeration as reactive and/or unstable. Relax your standards a bit, allow another atom or two, bump up the molecular weight, do any of those and you’re going to exceed anyone’s computational capacity. Update: the Berne group has just taken a crack at it, and managed a reasonable set up to 13 heavy atoms, with various simplifying assumptions to ease the burden. If you want to mess around with it, it’s here, free of charge).
Source:Â Corante
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BioFocus DPI to apply TET Technology in high-throughput screening campaigns
Last Updated on Sunday, 26 April 2009 05:10 Written by Editor Sunday, 26 April 2009 05:10
Saffron Walden, UK and Heidelberg, Germany; 24 April 2009 – BioFocus DPI, a leading provider of gene-to-candidate discovery services, and TET Systems Holding, a privately-held, German-based biotech company, announced today that they have entered into an agreement to apply TET System’s inducible gene technology in high-throughput screening campaigns performed for BioFocus DPI customers.
BioFocus DPI will offer TET Technology as part of its drug discovery screening service. Through this technology, the activity of individual genes can be controlled quantitatively and reversibly in cellular assays. This approach is particularly powerful in cases where the target is not well tolerated in the cells, since the protein will not be expressed until required for screening.
“The TET Technology allows us to build on the proven compound screening service that we offer clients. This powerful approach will benefit discovery programs that are hindered by difficult to express targets. Using this technology, we will be able to perform more efficient, extensive compound screening on these problematic targets,†commented Dr. Kate Hilyard, VP Biological Sciences, BioFocus DPI.
“We are very pleased to sign this agreement with BioFocus DPI, one of the leading drug discovery service providers worldwide. TET Technology has been used successfully for many years by most of the major pharmaceutical companies. Through this new partnership with BioFocus DPI, a broader range of pharmaceutical and biotechnology companies will gain access to TET System’s gene expression technology,†stated Dr. Ernst Boehnlein, CEO of TET Systems Holding and IP Merchandisers.
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Ligand and GlaxoSmithKline Collaboration Identifies New Lead Compound
Last Updated on Monday, 13 April 2009 10:29 Written by Editor Monday, 13 April 2009 10:29
SAN DIEGO, Mar 30, 2009 (BUSINESS WIRE) —-Ligand Pharmaceuticals Incorporated (NASDAQ: LGND: 2.98, -0.14, -4.49%) today
announced that it has identified a new lead for advancement in its
alliance with GlaxoSmithKline (NYSE:GSK). This newly identified lead
compound is from a program being evaluated as a potential treatment for
inflammatory indications identified through the collaboration. As a
result of this achievement, Ligand has earned a $500,000 milestone
payment from GSK.
Including this milestone, Ligand has received a total of $18.5 million
from GSK in connection with the alliance. Ligand is entitled to receive
success-based milestone payments from GSK, starting in the preclinical
research stage, for each drug development program and potentially up to
double-digit royalties on the sales of any product commercialized by GSK
under the multi-program alliance. The drug screening alliance with GSK
began in March 2006 with the goal of identifying and advancing novel
candidates in broad therapeutic areas.
“We are very pleased to see the continued progress with GSK under this
broad and productive discovery alliance,” said John L. Higgins,
President and Chief Executive Officer of Ligand Pharmaceuticals. “GSK
has been an excellent collaborator with Ligand through the years,
working initially on the discovery of PROMACTA(R: 24.08, -1.36, -5.35%), which was recently
approved, and now on multiple novel early-stage targets. These milestone
payments provide cash to fuel our business and represent the value and
caliber of the drug screening and research we provide our partners.”
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Ligand and GlaxoSmithKline Collaboration Identifies New Lead Compound
Last Updated on Monday, 13 April 2009 10:29 Written by Editor Monday, 13 April 2009 10:29
SAN DIEGO, Mar 30, 2009 (BUSINESS WIRE) —-Ligand Pharmaceuticals Incorporated (NASDAQ: LGND: 2.98, -0.14, -4.49%) today announced that it has identified a new lead for advancement in its alliance with GlaxoSmithKline (NYSE:GSK). This newly identified lead compound is from a program being evaluated as a potential treatment for inflammatory indications identified through the collaboration. As a result of this achievement, Ligand has earned a $500,000 milestone payment from GSK.
Including this milestone, Ligand has received a total of $18.5 million from GSK in connection with the alliance. Ligand is entitled to receive success-based milestone payments from GSK, starting in the preclinical research stage, for each drug development program and potentially up to double-digit royalties on the sales of any product commercialized by GSK under the multi-program alliance. The drug screening alliance with GSK began in March 2006 with the goal of identifying and advancing novel candidates in broad therapeutic areas.
“We are very pleased to see the continued progress with GSK under this broad and productive discovery alliance,” said John L. Higgins, President and Chief Executive Officer of Ligand Pharmaceuticals. “GSK has been an excellent collaborator with Ligand through the years, working initially on the discovery of PROMACTA(R: 24.08, -1.36, -5.35%), which was recently approved, and now on multiple novel early-stage targets. These milestone payments provide cash to fuel our business and represent the value and caliber of the drug screening and research we provide our partners.”
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New Model For Drug Discovery With Fluorescent Anesthetic Demonstrated
Last Updated on Monday, 13 April 2009 10:28 Written by Editor Monday, 13 April 2009 10:28
ScienceDaily (Apr. 8, 2009) — A collaboration of University of Pennsylvania and University of Wisconsin chemists and anesthesiologists have identified a fluorescent anesthetic compound that will assist researchers in obtaining more precise information about how anesthetics work in the body and will provide a means to more rapidly test new anesthetic compounds in the search for safer and more effective drugs.
The study is published online in the Proceedings of the National Academy of Sciences.
Using the fluorescing compound 1-aminoanthracene, or 1-AMA, the team developed a high-throughput assay to test for new anesthetic compounds. The assay will allow researchers to search for new anesthetic drugs and new molecular targets for anesthetics while at the same time creating high-resolution images of the compounds in action, a missing component that has hindered anesthetic research.
Researchers confirmed the compound as anesthetic after testing it successfully in tadpoles. By using transparent, albino tadpoles in the study, researchers were able to follow the fluorophore tag and image it in the brain of the immobilized, living animal.
Because the compound is fluorescent, researchers are able to image the compound in vivo in order to study its physiological effects. Where and how an anesthetic compound travels in an organism when administered and to what cells and concentrations are unknown in anesthetic administration and a key to improving efficacy and to reducing side effects. Because anesthetics bind weakly to their chemical targets, which may play a role in some of the unintended side effects, searching for new targets in the central nervous system is difficult.
“We don’t know much about how anesthetics work at a molecular level,†said Roderic G. Eckenhoff, vice chair for research and the Austin Lamont Professor of Anesthesiology and Critical Care at Penn’s School of Medicine. “Thus, the development of new anesthetics has become a stagnant field. This new tool will allow for the high-throughput screening of novel drugs.â€
Researchers from the School of Medicine and School of Arts and Sciences at Penn initiated the study in response to the health-care industry’s need for new and more powerful tools to discover and test new anesthetics and to learn more about how they work. The authors identified 1-AMA in a screen for compounds that bind to a cavity in horse spleen apoferritin, HSAF, that Eckenhoff and co-workers have shown to bind clinical anesthetics.
Researchers noticed a resemblance in the crystal structure of the apoferritin protein to that of the transmembrane region of the superfamily of ligand-gated channels that includes the GABA receptor. Anesthetics are known to positively modulate GABA signaling.
Because 1-AMA competes with other anesthetics to bind to apoferritin, researchers surmised that the protein likely binds to the same region of apoferritin as traditional anesthetics and thus shares their mechanism of action. Fluorescence of 1-AMA is enhanced when bound to apoferritin. Thus, displacement of 1-AMA by other anesthetics attenuates the fluorescence signal and allows determination of anesthetic affinity, that is, the drugs that bind tightly to the ferritin anesthetic site. In this way, 1-AMA fluorescence could be used to discover new anesthetics. This provides a unique fluorescence assay for compound screening and anesthetic discovery.
Using confocal microscopy to image the distribution of the protein, the team found that 1-AMA localizes largely in the brain and olfactory regions, unlike some general anesthetics which spread widely throughout the body. Ideally, clinical anesthetics would have a very focused target area in order to minimize systemic toxicity.
The Penn team will now collaborate with the National Chemical Genomics Center in Rockville, Md., to screen rapidly for novel anesthetic compounds, allowing for the screening of hundreds of thousands of new compounds per week.
“The 1-AMA compound opens up new avenues for identifying the relevant biomolecular targets of general anesthetics,†Ivan J. Dmochowski, assistant professor in the Department of Chemistry at Penn, said. “1-AMA appears to be specific in its binding to proteins and also in its in vivo localization, which should give us the opportunity to determine its mechanism of action,†he said. “We hope to be able to extend our findings to learn how current general anesthetics, such as propofol, work in human patients. There are many different and challenging aspects of trying to learn how anesthetics work that involve medicinal chemistry, biochemistry, molecular modeling, imaging, cell electrophysiology, pharmacology, neurobiology and animal physiology.â€
According to the study, 1-AMA increases the transmission potential of the body’s main neurotransmitter inhibitor, GABA. The compound also gives an appropriate dissociation constant, Kd 0.1 mM, for binding to the general anesthetic site in horse spleen apoferritin, meaning the compound is behaving as traditional general anesthetics would in humans.
In use for more than 150 years, general anesthetics are one of medicine’s greatest advances and yet there is still much to be learned about them. For many of the most commonly used anesthetic compounds, the molecular mechanisms behind their numbing effects and the way these compounds travel the pathways of the body remain poorly understood or altogether unknown.
According to the study team, anesthetics can bring on potentially harmful, even deadly, side effects for patients including rapid drops in blood pressure and heart rate, nausea and potentially irreversible cognitive problems, especially in older patients.
The study was funded by the National Science Foundation, the National Center for Research Resources, a Henry and Camille Dreyfus Teacher-Scholar Award, the National Institutes of Health and a University of Pennsylvania Institute for Medicine and Engineering Seed Grant.
The study was performed by Dmochowski and Christopher A. Butts of the Department of Chemistry at Penn, Eckenhoff and Jin Xib of the Department of Anesthesiology and Critical Care at Penn, Grace Brannigan and Michael L. Klein of Penn’s Center for Molecular Modeling and Abdalla A. Saad, Srinivasan P. Venkatachalan and Robert A. Pearce of the departments of Anesthesiology, Anatomy and Physiology at the University of Wisconsin.
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New Drug Shows Promise In Treating Drug-resistant Prostate Cancer
Last Updated on Monday, 13 April 2009 10:26 Written by Editor Monday, 13 April 2009 10:26
ScienceDaily (Apr. 11, 2009) — A new therapy for metastatic prostate cancer has shown considerable promise in early clinical trials involving patients whose disease has become resistant to current drugs.
Chemists and biologists at UCLA and colleagues at several other institutions, including Memorial Sloan-Kettering Cancer Center, have created a new drug to treat a particularly lethal form of the disease, known as castration-resistant prostate cancer, or CRPC. Also referred to as hormone-refractory prostate cancer, CRPC is resistant to further treatment by anti-hormone drugs such as Casodex and Eulexin.
In an article published April 9 in the advanced online edition of the journal Science, the scientists describe the development and testing of two novel compounds, MDV3100 and RD162, which block the androgen receptor (AR) in CRPC cells, and report results from clinical trials in which MDV3100 was found to lower prostate-specific antigen (PSA) levels — a marker for tumor growth — in men with CRPC.
The new, small organic molecule MDV3100 was “designed as a very strong antagonist of the androgen receptor to stop the growth of any prostate cancer that requires the AR for propagation, which includes most forms of prostate cancer,” said Michael Jung, UCLA professor of chemistry and biochemistry and a researcher at UCLA’s Jonsson Comprehensive Cancer Center, whose research group synthesized both MDV3100 and RD162.
The biology research was carried out in the UCLA departments of medicine, urology and pharmacology by Charles Sawyers and his research group; Sawyers has since moved to Memorial Sloan-Kettering Cancer Center in New York, where he serves as chair of the human oncology and pathogenesis program. The UCLA patents for both compounds were licensed by the pharmaceutical company Medivation Inc., which chose to test MDV3100 in clinical trials.
The drug has successfully completed Phase 1 and Phase 2 clinical trials, and the Food and Drug Administration has agreed to allow Medivation to begin what Jung described as “the pivotal Phase 3 clinical trials.”
The results of clinical studies with MDV3100 were described at the 2009 ASCO Genitourinary Cancer Symposium in February by the trials’ principal investigator, Dr. Howard Scher of Memorial Sloan-Kettering Cancer Center. In general, the drug, at 240 mg once a day, was very effective at lowering PSA levels and also in reducing the number of circulating tumor cells, without any significant toxicity.
“I think it is quite likely that the exciting results seen in the smaller population will also be evident in the larger Phase 3 trial and that the drug could be approved for use in the next few years,” said Jung, who is also a member of the California NanoSystems Institute (CNSI) at UCLA.
Of 30 men with anti-androgen–resistant prostate cancer who received low doses of MDV3100 in the multisite Phase 1/2 trial designed to evaluate safety, 22 showed a sustained decline in PSA levels, an indication that their cancer was responding favorably to the drug. This trial is still underway, and results from a total of 140 patients receiving higher doses of the drug will be reported within the next year, Sawyer said.
The Phase 3 clinical trial will evaluate the drug’s effect on survival in a large group of patients with metastatic prostate cancer.
MDV3100 and RD162 are second-generation anti-androgen therapies that prevent male hormones from stimulating the growth of prostate cancer cells. These new compounds appear to work well even in prostate cells that have a heightened sensitivity to hormones; that heightened sensitivity makes prostate cancer cells resistant to existing anti-androgen therapies.
Approximately 186,000 new cases of prostate cancer are diagnosed each year in the United States. The male hormones testosterone and dihydrotestosterone, which are also known as androgens, spur the growth of prostate cells, and drugs that block the receptors for these hormones are the most common treatment for the disease in its advanced, metastatic stage. Anti-androgen drugs, such as bicalutamide (Casodex), suppress the growth of cancer cells temporarily, but in most patients, the cancer ultimately develops resistance to drugs. Approximately 29,000 men in the United States die each year from the disease.
Prostate cancer becomes resistant to anti-androgen drugs when cancer cells begin to increase production of the androgen receptor, Sawyers said. When the level of androgen receptors on the cells’ surface reaches a certain level, the drugs that originally suppressed the cancer actually begin to stimulate cancer growth.
Because of this backlash effect, many scientists have questioned whether blocking the androgen receptor is a wise course of action. Sawyers and his colleagues, however, believe that blocking the receptor is critical to successful treatment. They set out to design a new generation of drugs that can block the androgen receptor without unwanted side effects, even when levels of the receptor are high.
Researchers in Jung’s and Sawyers’ laboratories based their designs on a drug that tightly attaches to the site on the androgen receptor that binds with testosterone. If that site is blocked, the hormone cannot bind to prostate cells and tell the receptor to stimulate growth. Using this initial drug as a chemical scaffold, the researchers synthesized nearly 200 slightly different versions of the drug. They tested each one in the laboratory on prostate cancer cells that had been engineered to produce high levels of androgen receptor.
This screening yielded MDV3100 and RD162, molecules which tightly bind to the androgen receptor and do not show the cancer-stimulating effect of bicalutamide and other current anti-androgen drugs. The molecules were good candidates for drugs, because they are readily absorbed into the blood when taken orally and they persist in the bloodstream. The researchers tested the new drugs’ effectiveness in mice with tumors derived from drug-resistant prostate cancer cells.
“To our delight, we found that these compounds caused very dramatic shrinkage of tumors in the mice,” Sawyers said. “While treating these animals with bicalutamide produced a modest effect on their tumors, the new drugs caused the tumors to shrink dramatically, and in some animals almost completely.”
Sawyers said the new drugs bind tightly enough to the natural hormone-binding site on androgen receptors to prevent most of them from functioning, even in cells with many androgen receptors.
The promising laboratory studies led Medivation to license the drugs for commercial development.
Medivation has received permission from the FDA for a large Phase 3 clinical trial of MDV3100 on about 1,200 patients with anti-androgen-resistant disease. This study will assess MDV3100′s effect on cancer survival and will take several years.
While the preliminary results are promising, Sawyers said his laboratory will continue to seek further improvements in drug therapy for prostate cancer.
“There were some men in the initial trial in which the drug didn’t work at all, and we want to find out why,” he said. “It may be because the drug is not potent enough to overcome resistance due to androgen receptor over-expression. Or it may be that the cancers in these men are not driven by the androgen receptor anymore. Also, there were men who initially received benefit from the drug but then relapsed, and their PSA levels came back up. We want to understand the mechanism of that relapse and to try to develop drugs that prevent that renewed resistance.”
For years, no treatment was available for CRPC; recently paclitaxel — a strongly cytotoxic drug — was approved.
In addition to Sawyers’ and Jung’s teams, researchers from the Oregon Health and Science University, the University of Washington and Medivation contributed to the research.
This research was supported by the National Institutes of Health, the Department of Defense, the Prostate Cancer Foundation and Medivation and was conducted through the Prostate Cancer Clinical Trials Consortium.
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Institute of Microbiology of the Chinese Academy of Sciences and TB Alliance Announce Partnership to Develop New Tuberculosis Drugs from Natural Sources
Last Updated on Wednesday, 1 April 2009 12:44 Written by Editor Wednesday, 1 April 2009 12:44
BEIJING & NEW YORK–(BUSINESS WIRE)–The Institute of Microbiology (IMCAS), a member institute of the Chinese Academy of Sciences, and the Global Alliance for TB Drug Development (TB Alliance), a not-for-profit product development partnership accelerating the discovery and development of new TB drugs, today announced a partnership to discover and develop promising, novel anti-tuberculosis agents from natural sources, including microbial metabolites and traditional Chinese medicines.
A pilot screen conducted by IMCAS identified 24 natural product extracts as having potential anti-tubercular activity. IMCAS and the TB Alliance will collaborate to further test these extracts, purify and identify the active components, and develop those that prove most promising. Additionally, IMCAS and the TB Alliance will work together to investigate traditional Chinese herbal medicines and purified compounds for biological activity against the Mycobacterium tuberculosis (M.tb) organism. Scientists in China have made significant contributions in developing new drugs from natural sources, as exemplified by the identification of Artemisinin, one of the most effective anti-malarial drugs, first isolated from a traditional Chinese medicinal plant. The deficiency in natural product screening directly against M.tb combined with China’s strong track record of successfully developing new drugs from traditional Chinese medicines, suggests such screenings are likely to yield novel active compounds.
Previously, a group of scientists including Professors Lixin Zhang, Deborah Hung and Eric Rubin of IMCAS, Broad Institute and Harvard University, respectively, worked together to investigate underlying mechanisms of M.tb, the bacterium that causes TB, with the intent to develop new TB drugs from natural sources to treat both drug-susceptible and drug-resistant TB. Modern technologies including high-throughput chemical screening, total genome sequencing, and the construction of systematic, comprehensive arrayed bacterial libraries were utilized in this process.
“This partnership reflects China’s increasing commitment to address the deadly TB epidemic, which has had such a devastating effect on so much of the world for so many years,†said Dr. Mel Spigelman, President and CEO, TB Alliance. “Bringing the best science in China together with the expertise of the TB Alliance is an example of the pooling of global resources necessary to save the millions of lives needlessly lost to TB every year.â€
Novel drugs are needed to work against drug-resistant TB, the more deadly and difficult-to-treat form of TB that is on the rise across the globe, including Asia. Drug resistance oftentimes emerges as a result of patients not completing the burdensome regimen currently used to treat drug-susceptible TB. The last class of new TB drugs was developed and approved in the 1960s. While the current treatment regimen for drug-susceptible TB is effective when administered properly, it must be administered over six to nine months. Treatment for multidrug-resistant tuberculosis (MDR-TB) usually takes a minimum of 18 months and only cures approximately half of those infected. New, faster-acting TB treatments can improve treatment of both drug-sensitive and drug-resistant TB, enhance compliance, lower relapse rates, reduce the growth of drug resistant TB, reduce health care costs and save millions of lives. The partnership between IMCAS and the TB Alliance is a fitting precursor to the three-day ministerial meeting of high MDR-/XDR-TB burden countries beginning tomorrow in Beijing.
“The fight against tuberculosis is a global endeavor. This partnership represents joint efforts by IMCAS and the TB Alliance in the development of new TB drugs from natural resources,†said Prof. Li Huang, Executive Deputy Director-General of the IMCAS. “Natural products have long been an important source of drugs for human medicine. The rich functionality and stereochemistry of natural products is without doubt one of their great strengths, providing both potency and selectivity. Taking advantage of its expertise in the exploitation of microbial resources, IMCAS has recently set up the Drug Discovery Center for Tuberculosis. The aim of the Center, led by Prof. Lixin Zhang, is to develop and deliver novel TB drugs that work quickly and can help prevent the problems of today’s drugs relating to compliance, drug resistance and TB-HIV co-infection.â€
The TB Alliance is leading the development of the most comprehensive portfolio of TB drugs in history, and is accelerating discovery, preclinical and clinical research of known and novel classes of antibiotics to shorten and simplify the treatment of tuberculosis, including MDR- and XDR-TB. The TB Alliance is committed to making all drugs developed by its research partnerships affordable and available to all who need them.
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AsisChem and Apredica Announce Strategic Alliance to Combine Complementary Drug Discovery Support Services
Last Updated on Wednesday, 1 April 2009 12:39 Written by Editor Wednesday, 1 April 2009 12:39
Watertown, Mass. (PRWEB) March 30, 2009 — AsisChem, Inc., a custom chemical synthesis and medicinal chemistry services provider, and Apredica, an ADME-Tox contract research laboratory, today announced a strategic alliance to provide drug-discovery support services to biotech, pharmaceutical, and non-profit research organizations around the world. The alliance provides Apredica and AsisChem’s clients immediate and convenient access to both companies’ core services: Apredica’s ADME-Tox services and AsisChem’s powerful, cost-effective small-molecule synthesis and analog library development.
“Our firms excel in our respective areas of expertise” said Grigoriy Rublev, AsisChem’s Chief Executive Officer. “The joint effort establishes an expanded menu of coordinated, complementary, high-value services that drug discovery teams can engage to accelerate drug development, improve cost efficiency, and increase program success rates,” he added.
“The combination of Apredica’s ADME-Tox services and AsisChem’s synthesis and medicinal chemistry capabilities means that now our customers can increase their cycle speeds,” said Katya Tsaioun, Ph.D., President of Apredica. “Direct communication of our ADME-Tox data back to AsisChem’s chemists means that discovery teams can develop their best lead compounds faster and submit their IND applications sooner.”
Chemical Synthesis in Drug Discovery
Organizations that advance their discovery programs beyond the identification of viable screening hits require synthesis and testing of up to hundreds of analogs during the hit-to-lead and lead-optimization stages to identify a viable clinical development candidate. Success often depends on testing a sufficiently large array of carefully selected analogs in an iterative process that is usually constrained by cycle times and budgets. AsisChem relies on its experienced pool of Ph.D.-level chemists and a low-cost infrastructure to deliver high-quality synthetic analogs with lower budgets and shorter timelines than its leading competitors can achieve. “We were able to synthesize more compounds than we expected based on offers from other custom synthesis companies” said Dr. Carlos E. Pedraza, a postdoctoral fellow at the Cleveland Clinic. “This gave us the opportunity to successfully explore more research avenues than we originally thought possible.”
ADME-Tox Profiling in Drug Discovery
Drug discovery and development programs see many drug candidates fail in clinical-trial stages. Many of these failures could have been avoided through the application of early ADME testing and toxicity profiling, which can quickly identify drug candidates with characteristics that would preclude regulatory approval. Early identification of these sure-to-fail candidates saves not only millions of dollars, but also months or years of research time that could have gone towards producing a successful drug candidate. Apredica works closely with clients to provide the data needed to reduce the risk of expensive, later stage failure, to increase the likelihood of drug development program success, and to accelerate the program towards IND. “More than any other CRO I have worked with, Apredica acts as a true collaborative partner and not simply a for-hire service provider. I have on many, many occasions benefited from Apredica’s guidance, help and advice, something I have generally not seen in other CROs” said Dr. Donald Kirsch, Vice President of Drug Discovery at Cambria Pharmaceuticals.
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GTCbio Announces its 4th Annual Assay Development and Screening Technologies Conference taking place
Last Updated on Wednesday, 1 April 2009 12:38 Written by Editor Wednesday, 1 April 2009 12:38
The goal of the 4th annual Assay and Screening Technologies Conference is to provide a forum for academics and professionals in the drug discovery industry to stay abreast of exciting new developments in assay technologies while exchanging ideas and developing more efficient approaches to the drug discovery and development process.
[USPRwire, Thu Mar 26 2009] GTCbio Announces its 4th Annual Assay Development and Screening Conference taking place June 8-9, 2009. As compounds derived from high throughput screening increasingly find their way into clinical trials, drug screening has become widely accepted as a critical step in the drug discovery process. After more than a decade of rapid growth, tremendous progress has been made in assay technology, laboratory automation, and informatics. These technological developments have not only facilitated a drastic increase in throughput and efficiency in drug screening, but have also provided novel solutions in other areas of drug discovery and development. As screening has also become prominent in biological research, screening facilities have become increasingly popular in academic institutions.
As the pharmaceutical industry continues to face the challenges of developing more new chemical entities and reducing the cost of R&D, the demand for novel technologies and creative approaches for improving the efficiency of screening has intensified. Cell-based assays used in compound screening and high-content screening technologies have gained popularity in the industry. Years of intensive research have finally resulted in label-free technologies in the drug screening market place. These technologies provide new ways of interrogating cellular and molecular binding events and enable orthogonal screening approaches to drug targets.
The goal of the 4th annual Assay and Screening Technologies Conference is to provide a forum for academics and professionals in the drug discovery industry to stay abreast of exciting new developments in assay technologies while exchanging ideas and developing more efficient approaches to the drug discovery and development process.
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First auto carbohydrate synthesiser
Last Updated on Tuesday, 24 March 2009 12:24 Written by Editor Tuesday, 24 March 2009 12:24
German researchers have unveiled the first fully automated carbohydrate synthesiser, which they hope will advance development of carbohydrate-based vaccines for the developing world.
The new machine was announced at this week’s meeting of the American Chemical Society in Salt lake City, Utah, and could significantly reduce the amount of time it takes for researchers to build complex carbohydrates for vaccine research. Currently, synthesis of multiple carbohydrates for screening causes a bottle neck in efforts to discover new carbohydrate-based vaccines.
‘A chemical synthesis of a single carbohydrate typically takes months to years,’ explains Peter Seeberger from the Max Planck Institute of Colloids and Interfaces, Potsdam. His team has now revealed a next generation synthesiser, building on an earlier partially automated model announced in 2001, that Seeberger says is ‘entirely reliable, very fast and can be operated by somebody with no experience of chemistry at all’. And when he says fast, he means fast: ‘we have repeated a synthesis of a carbohydrate that initially took two years in the lab in less than 20 hours.’ He also claims to have fixed protection and deprotection issues, major hurdles in carbohydrate synthesis, that plagued the earlier version of the synthesiser.
The concept of the machine is very simple, solid phase chemistry. The starting point is a polystyrene bead with a single sugar attached and ‘we add to that one sugar at a time like threading beads on a necklace,’ explains Seeberger. ‘The bead’s only role is to stop the sugar from being dissolved, and using this methodology we can build up chains between six and 15 sugars. The addition of each sugar takes about two hours, meaning that in 1.5 to two days we can make pure, useable quantities of carbohydrates.’ In a single run they can make 25-50mg of carbohydrate. Seeberger also claims that the sugar building blocks can be made easily in 50-100g bulk quantities.
Carbohydrates surround every cell in humans, bacteria and viruses and play a crucial role in the body’s immune response to disease-causing viruses and bacteria. They have been used for medicinal purposes before, including in some blockbuster vaccines used to inoculate small children against bacterial diseases, such as meningitis, explains Seeberger. The current vaccines are based on isolated carbohydrates – meaning drug companies have to grow bacteria, harvest the carbohydrates, isolate mixtures of compounds and put them into a carrier protein – and Seeberger is looking to simplify this process by using carbohydrates that can be chemically synthesised and therefore help drive down the cost of these vaccines.
The 2001 version of his machine was used to develop a carbohydrate-based vaccine for malaria, scheduled to enter clinical trials in 2010. Malaria kills two million children a year in the developing world, explains Seeberger, and ‘we have a cost target of under $1 per child’. Using their technique the team now have ‘approximately 15 carbohydrates that are entering different phases of development for potential clinical purposes such as tuberculosis.’
The price is pretty attractive too – according to Seeberger the machine itself will cost somewhere in the region of $25,000 (£17,000), approximately one quarter the price of the analogous peptide synthesiser owned by most labs.
Geert Jan Boons, University of Georgia, Athens, US, an expert in carbohydrate synthesis, says that this technology is ‘very sophisticated and has great potential’. Explaining that there is nothing similar available, he says ‘most complex carbohydrates are made in solution, and any solid phase chemistry that is done uses manual approaches – where you add the reagents one by one yourself.’ Seeberger’s fully automated system handles everything, including cooling and warming of each step as required, he adds. Boons does however say that he is not entirely convinced that the chemistry is yet robust enough to make every type of carbohydrate, but adds that Seeberger does claim to have fixed these issues in research he is yet to publish. ‘I think the biggest hurdle will be when he tries to make a bigger molecule,’ he explains, adding that the separation of the desired product from its isomeric compounds is another hurdle that needs to be overcome.
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Thermo Fisher Scientific Accelerates Drug Discovery Process with New Maybridge Quick2LeadT Compound Kits
Last Updated on Thursday, 19 March 2009 01:17 Written by Editor Thursday, 19 March 2009 01:17
TINTAGEL, England, (17 March 2009) – Thermo Fisher Scientific, the world leader in serving science, announced today that it has introduced a novel tool to accelerate hit-to-lead programmes in the drug discovery process. Its Maybridge Quick2Lead™ Compound Kits are designed to save time and money by enabling rapid compound library synthesis around bioactive “hits†emerging from screening assays. The kits are made up of pre-weighed, diverse building block selections, facilitating rapid capture of structure-activity (SAR) data from the closely related structural analogues within the library.
Quick2Lead Compound Kits are available as five functionality-based kits, with each one containing 48 carefully selected compounds. This enables the exploration of a wide area of chemical space to maximise credible SAR data acquisition for the successful conversion of an initial hit into a genuine, optimisable lead. Since these compounds are all pre-weighed, the kits are ready to use by simply adding solvent and transferring straight to a synthesiser.
The five functional groups available include: carboxylic acids, sulfonyl chlorides, amines, anilines and boronic acids. Each of these different functional groups is applicable to a wide range of tried and trusted parallel synthesis methodologies. Furthermore, although each kit taps into the hugely diverse Maybridge collection, they all include compounds from the top levels of the relevant Topliss Tree, thereby ensuring quality and rigour in interaction testing.
Each of the pre-selected compounds is supplied as 0.1mMol in a 5mL vial. This saves time and money at several levels — minimising stock, avoiding disposal and reducing storage footprint. The pre-selection process also avoids the “dead time†that can be experienced whilst waiting for multiple building blocks from internal and external sources. Maybridge Quick2Lead Kits arrive as a complete library, delivered rapidly ex-stock.
“Our aim with the Maybridge product range is to help shorten the discovery process, from screening to scale-up, and the introduction of our Quick2Lead Compound Kits is the latest addition to our broad product portfolio of pharmacophorically relevant compounds and services,†said Dr. Mick Durrant, Director of Business Development for Maybridge products at Thermo Fisher Scientific. “We recognise that identifying, sourcing and weighing building blocks to feed the library production process around an initial hit can be time consuming and expensive. Our new Quick2Lead Kits offer a novel approach to drive these costs down by providing pre-weighed, diverse building block selections which are simply ready-to-go.â€
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