Role of the National Cancer Institute in Acquired Immunodeficiency Syndrome-Related Drug Discovery

(NCI) is to facilitate drug dis-covery by the extramural cancer and acquired immunodeficien-cy syndrome (AIDS) research communities. This role is accom-plished in a variety of ways through grants programs, web-based informatics, provision of chemicals and natural product extracts, and screening services that will be described briefly in this ar-ticle. Recently, the NCI has begun efforts to bring together mo-lecular-targeted, high-throughput screening and extramural sites with chemical libraries of interest. This new initiative is de-signed to match emerging molecular targets and high-throughput assay technology with novel sources of chemical diversity in the extramural community. Shortly after recognition of the AIDS epidemic, the Devel-opmental Therapeutics Program (DTP) of the NCI was charged with developing a drug-screening program that might give rise to the discovery of novel therapeutics for the treatment of human immunodeficiency virus (HIV) disease. Beginning in 1987 and continuing through 1997, a functional screen for primary anti-viral treatments with the use of a cell-based assay system was in place. Details of the colorimetric-assay methodology and screen-ing strategy have been published (1,2). This screening program supported discovery of numerous lead compounds, from both natural and synthetic sources, many of which were subsequently demonstrated to be nucleoside and non-nucleoside reverse tran-scriptase inhibitors. A substantial number of novel natural prod-uct agents with anti-HIV activity have been isolated, including cyanovirin, a novel gp120-binding protein derived from a cul-tured blue-green alga (3). Detailed information on these mol-ecules may be found on the DTP web sit