Document 0972
 DOCN  M95A0972
 TI    An 'information-intensive' strategy for drug discovery in cancer and
       AIDS: relating cell cycle factors to patterns of drug activity (Meeting
       abstract).
 DT    9510
 AU    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
 SO    Proc Annu Meet Am Assoc Cancer Res; 36:A1813 1995. Unique Identifier :
       AIDSLINE ICDB/95609588
 AB    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.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY  Cell Line  *Drug
       Information Services  *Drug Screening Assays, Antitumor  Human
       *Information Systems  Neoplasms/*DRUG THERAPY  Software
       Structure-Activity Relationship  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).