September 15, 2003 | The NIH’s plan is inspired in part by Harvard University chemist Stuart Schreiber, a champion of the integration of chemistry with biology (see Conquering Infinity with Chemical Genetics, Feb. 2003 Bio-IT World, page 48).
Schreiber’s reputation is winning fans in high places in academia and industry. He recently became a founding faculty member of Eric Lander’s new Broad Institute (see Harvard and MIT’s Broad Vision for Genomic Medicine, July 2003 Bio-IT World, page 1). Harvard’s Institute of Chemistry and Cell Biology (ICCB), which Schreiber founded and co-directs, recently received funding from the National Cancer Institute (NCI)’s Initiative in Chemical Genetics (ICG). That effort centers around building a chemical library (ChemBank) to help accelerate drug discovery.
“Genomics can only take you so far,” says NCI’s Daniela Gerhard. “Being able to modulate the cell more easily is the next step.”
More than 15 groups have contacted ICCB to set up screening facilities, according to Schreiber protégé Caroline Shamu, head of screening at ICCB. Shamu says programs are in place at Case Western Reserve University, the University of Texas Southwestern, the University of Kansas, and The Rockefeller University, among others. Most of these groups are focused on studying gene function, but with an eye for drug candidates as well.
However, the first non-profit screening efforts in drug discovery are also popping up. For example, Harvard recently set up a Laboratory for Drug Discovery in Neurodegeneration, which does high-throughput screening, and has plans for a similar effort in oncology.
The National Institute of Neurological Disorders and Stroke recently established a screening program, and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is launching a chemical biology core facility. “We will utilize novel structural scaffolds for identifying new leads and optimize existing leads,” says Kenneth A. Jacobson, chief of the NIDDK’s molecular recognition section in the laboratory of bioorganic chemistry. “Small molecules have been underutilized at NIH,” he says. Jacobson’s group has two compounds in clinical trials.
Collins maintains the chemical library initiative is the logical next step for NHGRI: “The importance of small molecules in drug discovery and development is undeniable,” he says. But even Schreiber concedes that his particular approach, matching traditional screening with nontraditional molecules, is relatively unproven: Only a few clinical candidates have emerged so far. “It’s theoretically very attractive,” he says. “Let’s not fool ourselves that the pharmaceutical industry has already found all the therapeutic targets.”
Most pharmaceutical libraries have traditionally used similar guidelines for what makes a putative drug. According to Schreiber, the complexity of biology has hampered drug discovery, and more complex chemicals are needed to fill the missing space.
Jacobson says he’s not concerned that so few clinical candidates have emerged from Schreiber’s lab. “Many of the molecules Schreiber has come up with have unique biological properties,” he says. “That’s the initial proof to me.” -- M.B.
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