Sunesis Announces Research Progress in Targeting PTP-1B
SOUTH SAN FRANCISCO, Calif., April 28 /PRNewswire/ -- Sunesis Pharmaceuticals, Inc. announced today the discovery of a new class of drug fragments that interacts with the active site of Protein Tyrosine Phosphatase 1B (PTP-1B), a protein that is an important target for therapeutic intervention in Type 2 diabetes. These phospho-mimetic fragments, which could provide the core pharmacophores for novel inhibitors of PTP-1B, were discovered using an extension of the Company's Tethering technology termed "Breakaway Tethering." This extension allows Tethering to be used to identify drug fragments that bind to sensitive regions of a target protein such as a catalytic site.
Results of Sunesis' research are available in an advance online publication ("Discovery of a New Phosphotyrosine Mimetic for PTP-1B using Breakaway Tethering") of the May 14, 2003 edition of the Journal of the American Chemical Society (JACS). The abstract of the article can be found at pubs3.acs.org .
"Because its regulatory role in glucose metabolism in Type 2 diabetes is well validated, PTP-1B has been the focus of intense drug discovery efforts. To date, this target has proven challenging for the discovery of small molecule inhibitors that are potent, bioavailable and selective," stated James Wells, Ph.D., President and Chief Scientific Officer of Sunesis. "The use of Tethering and Breakaway Tethering provides new avenues for discovering small molecules. In addition to our active site work, we have also discovered a novel allosteric site on PTP-1B and have patent applications pending."
Steven James, Chief Business Officer of Sunesis, commented, "The published PTP-1B study is a strong demonstration of the scientific excellence we bring to important, validated disease targets that are available to be partnered, including targets addressing auto-immune diseases and HIV infection. For the PTP-1B program, we currently have active partnering discussions ongoing with a number of interested parties. Our self-funded discovery efforts are principally focused on progressing drugs for high-value oncology and immunology targets."
In February 2003, Sunesis was awarded a two-year, $500,000 research grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to support its PTP-1B research.
Technology Overview
Sunesis' technology platform reliably identifies binding ligands that other techniques such as high-throughput screening are too insensitive to find. Sunesis scientists screen libraries of drug-like fragments, fundamental building blocks of oral therapeutics, against validated targets that have been resistant to small molecule discovery. The basis for this approach is Tethering, a process in which the target selects fragments with binding affinity for a specific region on the target surface. By discovering drugs in pieces, Sunesis can efficiently search a chemical diversity space equivalent to hundreds of millions of compounds. Sunesis is using Tethering to discover oral therapeutics addressing a range of high-value enzyme targets and protein-protein interfaces, including cytokines, integrins, kinases, phosphatases, and proteases. |
