AUTOMOTIVE

The focus of the CRADA is Heat Shock Protein 90 (Hsp90), a target of considerable current scientific interest because of its potential pathophysiological role in cancer and other cell proliferative diseases and disorders. Under the terms of the agreement, Locus will create one or more series of molecules in silico that will be designed to have high specific affinity for Hsp90. The NCI will then conduct preclinical studies on the synthesized compounds to identify those that could ultimately be suitable for clinical study. Locus has a first option to an exclusive license on any inventions resulting from this collaboration. Heat Shock Proteins are a class of molecular "chaperones" which bind to and fold "client" proteins inside a cell. Disruption of the folding process by Hsp90 inhibition, for example, leads to degradation of these client proteins. Hsp90 client proteins include a number of key cancer-relevant targets such as the kinases Bcr-Abl, Raf-1, and Src, mutated p53, ErbB2, and the steroid hormone receptors. Because Hsp90 client proteins are so important in processes critical to the growth and survival of cancer cells (e.g., signal transduction and in transcription), Hsp90 inhibitors may serve as effective chemotherapeutic agents against a number of cancers. Dr. W. Douglas Figg, Senior Investigator and head of the Molecular Pharmacology Section and the Clinical Pharmacology Section at the NIH Center for Cancer Research, and Dr. Leonard Neckers, Senior Investigator of the Urologic Oncology Branch, are the NCI's Principal Investigators for this CRADA. Dr. William R. Moore, Jr., Locus' Vice President of Research and Development and Chief Scientific Officer, said: "We view this target as a great opportunity to combine our highly efficient drug design and lead optimization engine with the NCI's world class cancer biology and drug development capabilities to potentially accelerate the conventional timelines needed to develop new cancer therapies."