An 'information-intensive' approach to drug discovery for cancer and AIDS (Meeting abstract). NLM AIDSLINE Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Click here to return to AIDSLINE main menu
DonateNow
Print this Article


An 'information-intensive' approach to drug discovery for cancer and AIDS (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 35:A2197 1994. Unique Identifier : AIDSLINE ICDB/95603883
Weinstein JN; Myers T; Raghavan K; Buolamwini J; Anderson NL; Kohn KW; Scudiero DA; Monks AP; Zaharevitz D; Rubinstein LV; et al; Developmental Therapeutics Program, 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 potency against the various cell lines contains 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). This finding prompted us to develop the DISCOVER program package, which uses hierarchical clustering to integrate the data on a compound's pattern of potency with that on its 2D and 3D molecular structural features. To enhance the utility of this information, we have used 2D gel electrophoresis to characterize the cells with respect to expression of about 1,000 protein spots and have begun a parallel effort on expression of mRNA. These experimental and theoretical developments permit us to identify a molecular target or a mechanistic signature of activity in the screen and use it to interrogate the much larger database of over 300,000 compounds for which we have 2D and 3D structures. Since many of the compounds tested in the NCI's cancer screen have been tested in the AIDS screen as well, we have been able to construct an 'information interface' between the two programs.
Keywords: Acquired Immunodeficiency Syndrome/*DRUG THERAPY *Antineoplastic Agents *Drug Screening Assays, Antitumor *Drug Therapy, Computer-Assisted Molecular Structure Neoplasms/*DRUG THERAPY RNA, Messenger Tumor Cells, Cultured ABSTRACTKWDacquiredimmunodeficiencysyndrome/KWDdrugtherapyKWDantineoplasticagentsKWDdrugscreeningassays,antitumorKWDdrugtherapy,computer-assistedmolecularstructureneoplasms/KWDdrugtherapyrna,messengertumorcells,culturedabstract
950330
M9530851

Copyright © 1995 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1995. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1995. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .