Archive for the ‘Grants and Awards’ Category

By Kevin Davies

Genentech dominated the podium at the 2005 Pharma Achievement Awards in Boston this week. Genentech took five awards, including CEO and Chairman Arthur Levinson’s nomination as CEO of the Year. The Bay Area company also took three awards for the development and marketing of Avastin, including Industry Scientist of the Year to Mark Sliwkowski, Outstanding Biologic Drug Product, and Product Launch of the Year (together with Harrison and Star). Genentech also split a fifth award for Tarceva in the Outstanding Small Molecule Drug Product category.

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Researchers at the University of Kansas and the University of Kansas Medical Center have won an almost $8 million National Institutes of Health contract to find chemical compounds to develop into reversible male contraceptives that do not rely on steroids or affect bodily hormones.

Science & TechnologyLawrence, Kan. – infoZine – The five-year contract will allow the scientists from the two campuses to continue research and testing started in partnership with the NIH four years ago that has led to the development of promising chemical compounds. The KU team is one of only a few research groups in the world working to develop male contraceptives.

“We are in partnership with the NIH to develop chemical compounds that can eventually be turned into safe, effective and reversible male contraceptives,” said Gunda Georg, lead researcher on the project. “The NIH awarded this research contract to us because of the interdisciplinary and collaborative nature of our team, as well as the technology and laboratories KU and KUMC have for testing.”

Georg is also director for the Center for Drug Discovery at the Higuchi Biosciences Center on the Lawrence campus. The other primary members of her team are Joseph Tash, associate professor of molecular and integrative physiology at KUMC; Qi-Zhuang Ye, research professor at the Higuchi Biosciences Center; and Ernst Schonbrunn, assistant professor of medicinal chemistry.

In its work under the previous NIH contract, the KU team identified a chemical compound they named Gamendazole that caused temporary infertility in male rats by affecting sperm production, Georg said. Gamendazole, on which KU has filed a patent application, emerged from more than 100 compounds tested.

“The KU team has identified a dose of Gamendazole that caused 75 percent of the rats to lose fertility in week three after taking the compound and 100 percent of the rats to become completely infertile in week four and five,” Georg said. “Partial fertility begins to return to the rats in week six.”

The group also focused on finding novel inhibitors of key enzymes that either have an important role in sperm development or motility, Georg said. Finding chemical compounds to temporarily deactivate the enzymes so that the sperm do not fully develop or cannot move to cause pregnancy is the key objective of the research.

“We need to find compounds that are potent, selective and can be developed to be taken orally,” said Tash. “We do not want a compound to affect other enzymes in the body. We want to specifically target the right enzyme and nothing else.”

As part of the new NIH contract, hundreds of thousands of compounds will be tested on the key enzymes to see which ones might affect them. About 100,000 of those compounds will come from KU. The NIH will supply the rest.

KU was able to win the contract, in part, because of the research facilities available at the university, including the High Throughput Screening Laboratory, under the direction of Ye and a part of the Life Sciences Research Laboratories at 1501 Wakarusa Drive. While High Throughput Screening (HTS) technology is more common in private industry, KU is one of the few universities in the nation to have one, Georg and Schonbrunn said. Without the HTS lab, screening hundreds of thousands of compounds could take up to a year, but with the technology, screening time is dramatically reduced.

All the testing of compounds to date has taken place with rats and in test tubes. In the case of Gamendazole, human clinical trials could take place in three to four years with the approval of federal regulators.

“Through our research, we now know a great deal more about the male reproductive system,” Tash said. “We know what we might be able to do in this area and what enzymes we can target. The science has come to the point that we can say with some confidence that a reversible male contraceptive can be developed.”

Award is part of NIH effort to empower public sector to speed up medical discoveries

By Lisa Rossi, Pitt Chronicle

Pitt’s School of Medicine has received $9 million from the National Institutes of Health (NIH) to establish the University of Pittsburgh Molecular Libraries Screening Center (UP-MLSC).

The center is one of nine in the nation that will create the most sophisticated methods for rapidly assessing hundreds of thousands of compounds for their biological activities and therapeutic potential—a capability that has until now been limited almost exclusively to pharmaceutical companies. Moreover, to help speed the use of promising targets for drug development, all information collected by the centers will be freely available to the entire scientific community through PubChem, a comprehensive database that has been established by NIH.

As part of NIH’s Roadmap, which has as its overarching theme “New Pathways to Discovery,” NIH has allocated $88.9 million over the next three years to create the Molecular Libraries Screening Centers Network (MLSCN). NIH selected nine outside institutions as pilot centers to be included in the network, as well as NIH’s Chemical Genomics Center. Each center will work to develop the necessary tools conducting so-called high throughput screenings of molecules—which by the third year will allow each center to screen up to 100,000 molecule compounds using 20 different approaches, or assays, that help determine how these compounds interact with molecular targets, within cells, and are involved in regulating events that may be the root cause of different diseases.
Pitt’s center takes advantage of close ties between the School of Medicine’s Department of Pharmacology and the School of Arts and Sciences’ Department of Chemistry, along with new facilities devoted to drug discovery in the newly constructed Biomedical Science Tower 3. It also represents a unique collaboration with neighboring Carnegie Mellon University and with Sandia National Laboratories in Albuquerque, N.M., and provides the UP-MLSC unique expertise in design and development of novel probes that use fluorescence and other optical imaging techniques.

John S. Lazo, the Allegheny Foundation Professor of Pharmacology in Pitt’s medical school and principal investigator of the UP-MLSC, said: “As a pilot center in the Molecular Libraries Screening Centers Network, we will be able to exploit and expand our existing strengths for developing and implementing methods for the detection, characterization, and refinement of small molecules that have attractive biological and pharmacological properties and may eventually be further developed as therapeutic approaches to treating various diseases and conditions.”

Lazo will direct a core of UP-MLSC devoted to assay implementation. Andreas Vogt, research assistant professor of pharmacology in Pitt’s School of Medicine, will focus on high throughput screening, exploiting Pitt’s existing expertise in screening compounds in the context of whole cells. Peter Wipf, University Professor in Pitt’s Department of Chemistry and coprincipal investigator, will lead the new center’s synthetic chemistry core; the focus of that core will be to further improve and refine compounds designated as being the most promising to better target the specific errors that occur on the smallest of scales yet have profound effects on the development of disease. Mark D. Rintoul, manager of computational biology at Sandia National Laboratories, will direct UP-MLSC’s informatics core.

An NIH steering committee for the MLSCN, of which Lazo will be a member, will determine which of the most promising methods for screening molecules will be pursued and select from among its network of funded pilot centers those that will develop and implement these particular assays.

The National Institutes of Health (NIH) today announced it is awarding $88.9 million in grants to nine institutions over three years to establish a collaborative research network that will use high-tech screening methods to identify small molecules that can be used as research tools. Small molecules have great potential to help scientists in their efforts to learn more about key biological processes involved in human health and disease.

“This tremendous collaborative effort will accelerate our understanding of biology and disease mechanisms,” said Elias A. Zerhouni, M.D., NIH Director. “More importantly, it will, for the first time, enable academic researchers to explore novel ideas and enable progress on a broad front against human disease.”

For example, the broad-based screening effort will eventually enable researchers to explore the hundreds of thousands of proteins believed to be encoded by the approximately 25,000 genes in the human genome. To date, only a few hundred human proteins have been studied in detail using small molecule probes.

Certain small organic chemical compounds, also referred to as small molecules, can be valuable tools for understanding the many important cellular events involved in health and disease, which is key to identifying possible new targets for diagnosis, treatment and prevention. To date, most useful small molecules have been found serendipitously. The molecular libraries screening program is an effort by NIH to take an efficient, high-throughput approach toward the discovery of many more useful compounds.

The Molecular Libraries Screening Centers Network is being developed through the NIH Roadmap for medical research. Specifically, the network is part of the Roadmap’s “New Pathways to Discovery” initiative, which has set out to advance the understanding of biological systems and build a better “toolbox” for medical researchers in the 21st century. The network is funded by all of the institutes of the NIH and co-administered by the National Institute of Mental Health (NIMH) and the National Human Genome Research Institute (NHGRI) on behalf of NIH. The operation of the network will be overseen by a project team made up of staff from NIH’s 27 institutes and centers.

Data generated from the high-throughput assays conducted at the screening centers will be made available to researchers in both the public and private sectors through the PubChem database (http://pubchem.ncbi.nlm.nih.gov/), created and managed by the National Library of Medicine at NIH. The network’s first screening center, the NIH Chemical Genomics Center (NCGC), was established in June 2004 by the NHGRI’s intramural program to jumpstart the roadmap effort. Another critical component of the network is the Molecular Libraries Small Molecule Repository, located in San Francisco at Discovery Partners International, a drug discovery research firm. The repository houses the collection of small molecules that will be used for screening by the centers. Already, the repository has acquired nearly 100,000 compounds that are being utilized by the NCGC.

“This new Screening Centers Network will be the engine of discovery in the NIH Roadmap Molecular Libraries initiative,” said NIMH Director Thomas R. Insel, M.D. “Using the compounds from the Molecular Libraries Small Molecule Repository and supported by the informatics capabilities of PubChem, the MLSCN should provide researchers with many new chemical tools to explore how cells function at the molecular level.”

“This collaborative screening effort will enable academic and government researchers to contribute in a much more vigorous way to an understanding of the mechanisms of disease, and even to the identification of potential targets for new therapies. Central to this effort are the databases supporting the network, which will allow us to tie together data from diverse fields of science in ways not previously brought to bear on important health problems,” said NHGRI Director Francis S. Collins, M.D., Ph.D.

The nine institutions receiving grants as part of the Molecular Libraries Screening Centers Network (MLSCN) are:

* Columbia University Medical Center, New York, New York; James Rothman, Principal Investigator; MLSCN Center at Columbia University
* Emory University, Atlanta, Georgia; Raymond Dingledine, Principal Investigator; Emory Chemistry-Biology Center in the MLSCN
* Southern Research Institute, Birmingham, Alabama; Gary Piazza, Principal Investigator; Southern Research Molecular Libraries Screening Center (SRMLSC)
* The Burnham Institute, La Jolla, California; John Reed, Principal Investigator; San Diego Chemical Library Screening Center
* The Scripps Research Institute, La Jolla, California; Hugh Rosen, Principal Investigator; Scripps Research Institute Molecular Screening Center
* University of New Mexico Albuquerque, Albuquerque, New Mexico; Larry Sklar, Principal Investigator; New Mexico Molecular Libraries Screening Center
* University of Pennsylvania, Philadelphia, Pennsylvania; Scott Diamond, Principal Investigator; The Penn Center for Molecular Discovery
* University of Pittsburgh at Pittsburgh, Pittsburgh, Pennsylvania; John Lazo, Principal Investigator; University of Pittsburgh Molecular Libraries Screening Center
* Vanderbilt University, Nashville, Tennessee; C. David Weaver, Principal Investigator; Vanderbilt Screening Center for GPCRs, Ion Channels, and Transporters

About NIH
The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — is comprised of 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

About the NIH Roadmap for Medical Research
The NIH Roadmap is a series of new initiatives designed to pursue major opportunities and gaps in biomedical research that no single NIH institute could tackle alone but which the agency as a whole can address to make the biggest impact possible on the progress of medical research and to catalyze changes that will serve to transform new scientific knowledge into tangible benefits for public health. Additional information about the NIH Roadmap can be found at its Web site, www.nihroadmap.nih.gov.

About NIMH and NHGRI
NIMH and NHGRI co-lead the Molecular Libraries Roadmap Initiative and are among the 27 institutes and centers at NIH. NIMH works to reduce the burden of mental illness and behavioral disorders through research on mind, brain, and behavior. Additional information about NIMH can be found at its Web site, www.nimh.nih.gov. NHGRI supports the development of resources and technology that will accelerate genome research and its application to human health. Information about NHGRI can be found at its Web site, www.genome.gov.