An 'information-intensive' strategy for drug discovery in cancer and AIDS: relating cell cycle factors to patterns of drug activity (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

An 'information-intensive' strategy for drug discovery in cancer and AIDS: relating cell cycle factors to patterns of drug activity (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A1813 1995. Unique Identifier : AIDSLINE ICDB/95609588
Myers TG; Weinstein JN; Raghavan K; Buolamwini J; Anderson NL; O'Connor P; Kohn KW; Scudiero DA; Monks AP; Friend S; et al; Devel. Therapeutics Program DCT, NCI, Bethesda, MD 20892

Abstract: The NCI Developmental Therapeutics Program screens more than 10,000 compounds a year against a panel of 60 human cancer cell lines in vitro. A compound's 'signature' pattern of relative activity against the various cell lines has been shown to contain unexpectedly rich information about its mechanisms of action at the molecular level (Paull et al, JNCI 81:1088 1989; Weinstein et al, Science 258:447 1992). We have since then developed the discovery program package to integrate information on (1) the patterns of activity; (2) 2-D and 3-D molecular features in the NCl's Drug Information System (DIS) database of greater than 400,000 compounds; (3) an increasing repertoire of defined molecular targets and modulators of drug action in cell lines of the screening panel. Among those cellular features are a number of cell cycle factors, including p53 status and G1 and G2 checkpoint control. Also included is a coherent 2-D gel database of 151 protein spots for each of the 60 cell lines. These experimental and theoretical developments permit us to identify a molecular target or a signature of activity in the screen and use it to interrogate structures in the DIS database. In particular, we have asked how p53 and checkpoint status affect the relative activities of a large number of drug classes.

Keywords: Acquired Immunodeficiency Syndrome/*DRUG THERAPY Cell Line *Drug Information Services *Drug Screening Assays, Antitumor Human *Information Systems Neoplasms/*DRUG THERAPY Software Structure-Activity Relationship ABSTRACT
951030
M95A0973

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