Bio Screening Industry News

National Cancer Institute Chemical Biology Consortium to coordinate academic, private and government cancer drug discovery efforts

BIRMINGHAM, Ala., Aug. 20 /PRNewswire-USNewswire/ — Southern Research Institute today announced that it has been selected as one of 11 organizations to help establish the National Cancer Institute’s (NCI) Chemical Biology Consortium (CBC)–a program meant to coordinate and accelerate the discovery and development of new therapeutic agents to treat cancer patients. Southern Research will establish one of NCI’s five Comprehensive Chemical Biology Centers at its Birmingham campus.

“We are very pleased that Southern Research was selected to participate in this new program to expedite and coordinate the discovery and development of new cancer therapies,” said W. Blaine Knight, Ph.D., vice president of Drug Discovery and Principal Investigator of this effort at Southern Research. “Cancer accounts for nearly one out of every four deaths in this country and the National Institutes of Health estimate that the overall costs of cancer last year were more than $228 billion for health expenses and lost productivity. The search for newer and better drugs is never-ending, and something cancer patients and their families depend upon.”

Southern Research has a remarkable cancer-fighting track record having already discovered six FDA-approved drugs currently used in the treatment of cancer–amifostine, fludarabine, dacarbazine, lomustine, carmustine and clofarabine–with seven additional drugs in late stage preclinical and early clinical trials. Scientists at Southern Research have also evaluated approximately 50 percent of all FDA-approved cancer drugs currently available for patients.

“Our experience in cancer research and our track record in drug discovery were clearly recognized by our selection as a Comprehensive Center in the CBC consortium,” said John A. Secrist III, Ph.D., president and CEO of Southern Research. “We look forward to partnering with the federal government as it accelerates cancer drug discovery.”

As a Comprehensive Chemical Biology Center, Southern Research will focus on numerous aspects of preclinical drug research from target discovery, assay development, high throughput screening, structural/computational chemistry, and biology, through lead optimization and preclinical development. In addition Southern Research has an extensive compound library that will be made available for the CBC effort.

Dr. Knight says that work is expected to begin immediately.

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 Dept. of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.

About the Chemical Biology Consortium

The CBC will establish an integrated network of chemical biologists, molecular oncologists, and compound screening centers from government, academia, and eventually from industry. The drug discovery strategy of the CBC is to expand current NCI programs by providing a coordinated focus on therapeutic opportunities in high-risk, under-represented areas, significantly advancing the discovery of novel compounds active against specific molecular and genetic cancer targets. CBC efforts will include recruiting extramural investigators with specialized expertise in novel discovery platforms as well as medicinal chemistry, chemical biology, molecular oncology, and other areas of drug discovery and development. The CBC will be centrally managed to coordinate the selection of targets and screening for agents that interact with these targets, and will then use an iterative development process to design and optimize drug “hits” into “leads.” The CBC will benefit from access to the NCI’s late-stage drug development resources and expertise.

The program is being developed by NCI’s Division of Cancer Treatment and Diagnosis (DCTD), in conjunction with NCI’s Center for Cancer Research (CCR) and the NCI Director’s Office, with guidance from external advisory panels. This effort will be managed by the NCI’s Experimental Therapeutics (NExT) Program. SAIC-Frederick, Inc. (SAIC-F) will provide support for the key operational and technical aspects. It is envisioned that this Consortium will provide cutting-edge chemical tools for probing complex biochemical signaling pathways and will serve as the starting point for the elaboration of first-in-class targeted therapies. The long-term vision of the CBC is to bridge the gap between basic scientific findings and NCI-supported clinical research to facilitate the discovery and development of new agents to treat patients with cancer.

Participants will have an unparalleled opportunity to participate in a highly collaborative drug discovery partnership with the National Cancer Institute (NCI). Using state-of-the-art communication, data-sharing and project management tools, the CBC will effect a paradigm shift in the use of public-private partnerships to translate knowledge from leading academic institutions into ground-breaking new drug candidates for patients with cancer.

About Southern Research Institute

Southern Research Institute is a nonprofit 501(c)3 scientific research organization that conducts preclinical drug discovery and development, and advanced engineering research in materials, systems development, environment and energy. Our more than 550 scientific and engineering team members support clients and partners in the pharmaceutical, biotechnology, defense, aerospace, environmental and energy industries. Southern Research is headquartered in Birmingham, Ala., with facilities in Wilsonville, Ala., Anniston, Ala., Frederick, Md., and Durham, NC and offices in New Orleans, La., Washington, DC and Kiev, Ukraine. For more information about Southern Research and its capabilities and accomplishments, visit www.SouthernResearch.org.

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.”

“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.”

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.”

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.”

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:  vanderbilt.edu

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.”

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?”

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.”

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

Boston, MA - A drug that can selectively target and kill the stem cells that drive the growth of tumors has been identified for the first time by scientists who searched more than 16,000 compounds to find it.

Researchers at Massachusetts Institute of Technology and the Broad Institute looked for compounds that could destroy the stem cells, which often resist conventional cancer treatment. One, salinomycin, cut the number of stem cells at least 100 times more than did Bristol-Myers Squibb Co.’s Taxol, a common chemotherapy medicine, according to a report on the findings published today in the journal Cell.

The researchers will conduct further testing of salinomycin in animals to assess its potential to treat humans, said Piyush Gupta, a researcher at the Cambridge, Massachusetts-based Broad Institute and co-author of the study. While the outcome of that research is unknown, he said, the work has strengthened a theory that stem cells fuel cancer and may have created a way to find effective drugs.

“We now have a method that researchers anywhere in the world can use to find agents that can kill cancer stem cells and potentially treat cancer,” Gupta said today in a telephone interview.

Stem cells appear to fuel the growth of several kinds of cancer including breast, lung and brain tumors, according to studies done in recent years. The cells are resistant to standard cancer therapy, so finding a way to thwart them is important, said Judy Lieberman, a professor of pediatrics at Harvard Medical School who researches cancer stem cells.
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‘These Are the Cells’

“These are the cells that are the important cells and if you don’t eliminate them, the tumors can grow back and recur,” Lieberman said today in a telephone interview. “Any way you can figure out to specifically target the cancer stem cells is going to fill an important gap in the therapies we have at hand.”

Lieberman wasn’t involved in the report published today.

Scientists at universities and biotechnology companies including Infinity Pharmaceuticals Inc. of Cambridge, Massachusetts, and Australia’s ChemGenex Pharmaceuticals Ltd. are working to develop treatments to block the stem cells. Findings released in 2007 showed that one marketed anti-cancer drug, GlaxoSmithKline’s Tykerb, reduced the number of cancer stem cells and helped eliminate the disease in some breast cancer patients.

Tumor-Initiating Cells

Research by Jenny Chang at the Baylor College of Medicine has shown that after breast-cancer patients received chemotherapy and hormone treatments, the remaining tumors had a greater percentage of malignancy-initiating cells, the cancer stem cells, than before.

The researchers at MIT and Broad grew cancer cells from breast tumors in a way that increased the number of stem cells. They then used rapid screening techniques to test 16,000 commercially available chemical compounds. They identified 32 candidates before settling on salinomycin as the most potent.

They also tested the compound in mice in two ways. First, they exposed breast cancer stem cells in laboratory dishes to salinomycin and Taxol and tallied how many cells they would need to inject in a mouse to trigger a tumor. It took many more of the salinomycin-treated cells to spur cancer, showing that the compound was inhibiting cancer development, Gupta said.

Second, they induced tumors in mice and treated them with the two drugs. While both drugs exerted “significant anti-tumor effects,” the mice treated with Taxol had a greater proportion of cancer stem cells left in the remaining tumor. Taxol enriched the population of cancer stem cells and salinomycin reduced it, Gupta said.

“We have now a systematic way to look for compounds that selectively kill cancer stem cells,” Gupta said. “We’ve taken a lot of the serendipity out of the equation.”

The research was funded partly by the National Cancer Institute.
Source: vosizneias.com

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

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.

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

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.

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

Martinsried, Germany, April 29, 2009 / b3c newswire / - Kinaxo Biotechnologies GmbH has successfully applied its Cellular Target Profiling® technology to identify the protein kinase mTOR as a new cellular target of celecoxib (Celebrex®, Pfizer). Celecoxib is a non-steroidal, anti-inflammatory Cox-2 inhibitor approved for the treatment of osteoarthritis, rheumatoid arthritis and acute pain. In addition, celecoxib’s anti-proliferative effect has earned it a place in numerous clinical trials against several malignancies.

Link to the news release
http://www.b3cnewswire.com/popup.php?id=149

About KINAXO
Kinaxo Biotechnologies GmbH is a privately-held biotechnology company based in Munich/Martinsried, Germany. We offer advanced chemical proteomics and phosphoproteomics services to support lead compound selection, target deconvolution, drug reprofiling, and off-target toxicity assessment. Kinaxo has several ongoing collaborations, including with Boehringer Ingelheim, Johnson & Johnson and Takeda.

ScienceDaily (Mar. 27, 2009) — Metabolites are molecular fingerprints of what your cells are up to and Dr. Arun Sreekumar wants to know the impression made by cancer.

You’ve likely heard about metabolites; your physician probably screens for some known ones such as triglycerides or cholesterol at your annual physical. Scientists suspect we have about 3,000 metabolites that come from our food or are synthesized from different compounds in our bodies.

Dr. Sreekumar, a cancer researcher at the Medical College of Georgia Cancer Center, wants those screens of the blood or urine to also detect early signs of cancers such as leukemia, bladder, kidney and breast when the chance for cure is best.

He’s already begun to identify metabolites that indicate not only the presence of prostate cancer, but its aggressiveness, a tool that could help tailor optimal treatment. The search began in men at risk: those with elevated prostate specific antigen, or PSA, levels. A PSA test along with a digital rectal exam is today’s standard for prostate screening so physicians typically do both in men age 50 and older. But PSA levels are actually better at helping determine if prostate cancer has returned, Dr. Sreekumar says.

Elevated levels of PSA, a protein, are not always predictive of cancer, which means a lot of men get unnecessary biopsies. PSA measurements also can’t distinguish between tumors that have a good outcome versus those with a poor one.

“The physician does not really have the tools in hand to really say that this tumor will spread to other organs or not.” says the Georgia Cancer Coalition Distinguished Cancer Scholar. “We want to find clinical markers that supplement PSA.”

Aggressiveness is a major factor in prostate cancer treatment. In fact some men with slow growing disease likely won’t even need treatment. So he wants to provide a complement of biomarkers that accurately diagnose and categorize the disease then help monitor success of treatment. These early studies indicate a urine test may one day be possible to do just that.

He and colleagues at the University of Michigan reported in the Feb. 12 issue of Nature what appears to be one of the first metabolites implicated in cancer invasion. They looked at 1,126 metabolites in 262 samples taken from men with high PSA levels. They consistently found elevated levels of the amino acid sarcosine in the prostate tissues of men with cancer; levels were highest in what appeared to be the most aggressive tumors.

Sarcosine, a modified form of the amino acid glycine, was a known entity but its function was unclear. Scientists thought it might be a dumping ground for excess methyl groups needed to enable chemical changes of genes, proteins and other body components that can affect what and how much they do.

This process called methylation can be a good thing – like when it’s helping an embryo develop – but when it goes badly, it can cause disease such as cancer. While sarcosine’s dumping role seemed to protect from cancer, the Michigan scientists found its action actually helps induce tumors. In fact, when they added it to prostate cancer cells, the cells became more aggressive. Exactly how that process works is still under study but the findings were pretty consistent.

“When we looked at patients with metastatic disease, sarcosine levels were sky high compared to patients with localized tumors,” says Dr. Sreekumar. “It’s enabling invasion.”

Because cancer and people are both very heterogenous, measures need to be taken in larger population samples, he says. Also, they found a small group of patients with negative biopsies and high sarcosine levels. “We don’t know how many of them have missed cancer,” says Dr. Sreekumar who joined the MCG faculty in February.

These are among the reasons he believes in strength in numbers. “In the real world of biomarkers, you want 100 percent sensitivity. If the patient has cancer, you want to pick it up. We need to have a kind of multiplex test where you can test for say10 different entities and have a greater confidence that what you are stating about the tumor is true. Our goal is to develop such a panel and research on sarcosine is a first step toward achieving this.”

In his new position at MCG, he’s looking to expand the number of metabolites known to be predictive of prostate and other cancers. In prostate cancer, he’s beginning with follow up on other metabolites identified in the Michigan study in which researchers identified a total of six metabolites, including sarcosine, linked to increased tumor progression. A total of 89 metabolites were different in metastatic prostate cancer compared to localized disease.

He’s excited about what metabolites will one day tell cancer physicians and patients but adds that they are just a piece of what our bodies can tell us about a potential cancer growing inside. Scientists also need to continue to look at genes expressed by tumors and the proteins expressed by those genes to get the bigger picture. “It’s basically a systems approach you need to take,” he says.

The young scientist has worked with all those pieces in his relatively short career. He started his postdoctoral fellowship at the University of Michigan in1999, when the ability to look at gene expression was new. With his mentor, Dr. Arul M. Chinnaiyan, director of Michigan Center for Translational Pathology, Pathology Research Informatics and Cancer Bioinformatics at Michigan, he helped develop the next step: the ability to look at expression of hundreds of proteins at a time, instead of a handful, an important advance in light of the fact that there are about 1 million proteins. Recently they were among the first to venture into the world of metabolites, which are made by proteins.

“Previous technology was looking at a cell from a narrow perspective and cells never act in isolation, proteins never act in isolation, they always form complexes, act in pathways,” Dr. Sreekumar says.

His inspiration to follow those pathways is a fellow Ph.D. student who died too young and quickly of an aggressive leukemia and the fact that cancer is a leading cause of death worldwide.