Clinical trials to begin on designed AIDS drug

Abstract

Researchers have used structure-based drug design to successfully engineer greater bioavailability and increased potency into a potential anti-AIDS drug. The drug, designated VX-478, is an orally bioavailable inhibitor of human immunodeficiency virus (HIV) protease, a key enzyme in the life cycle of the virus. VX-478 was designed by scientists at Vertex Pharmaceuticals, Cambridge, Mass. Researchers from Burroughs Well-come, Research Triangle Park, N.C., and Vertex presented detailed preclinical data on the drug for the first time last month at the 2nd National Conference on Human Retroviruses & Related Infections, in Washington, D.C. (C&EN, Feb. 6, page 7). Burroughs is Vertex's development partner for VX-478. In addition, Vertex scientists recently reported the X-ray crystal structure of the inhibitor bound to HIV protease [ J. Am. Chem. Soc., 117 ,1181 (1995)]. The structure determination was carried out by Vertex scientists Eunice E. Kim, Chris T. Baker, Maureen D. Dwyer, Mark A. Murcko, B. Govinda Rao...