PMID: 9538518Apr 16, 1998Paper

Mining the NCI anticancer drug discovery databases: genetic function approximation for the QSAR study of anticancer ellipticine analogues

Journal of Chemical Information and Computer Sciences
L M ShiJ N Weinstein

Abstract

The U.S. National Cancer Institute (NCI) conducts a drug discovery program in which approximately 10,000 compounds are screened every year in vitro against a panel of 60 human cancer cell lines from different organs of origin. Since 1990, approximately 63,000 compounds have been tested, and their patterns of activity profiled. Recently, we analyzed the antitumor activity patterns of 112 ellipticine analogues using a hierarchical clustering algorithm. Dramatic coherence between molecular structures and activity patterns was observed qualitatively from the cluster tree. In the present study, we further investigate the quantitative structure-activity relationships (QSAR) of these compounds, in particular with respect to the influence of p53-status and the CNS cell selectivity of the activity patterns. Independent variables (i.e., chemical structural descriptors of the ellipticine analogues) were calculated from the Cerius2 molecular modeling package. Important structural descriptors, including partial atomic charges on the ellipticine ring-forming atoms, were identified by the recently developed genetic function approximation (GFA) method. For our data set, the GFA method gave better correlation and cross-validation results (R2 an...Continue Reading

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Citations

Jul 8, 2010·Journal of Molecular Modeling·João Paulo S FernandesCarlos A Brandt
Nov 8, 2003·Bioorganic & Medicinal Chemistry·Albert R CunninghamBilly W Day
Jan 28, 2004·Comptes rendus biologies·John N Weinstein, Yves Pommier
Mar 12, 2002·Bioorganic & Medicinal Chemistry·Mahindra T Makhija, Vithal M Kulkarni
Mar 4, 2000·Nature Genetics·U ScherfJ N Weinstein
Feb 14, 2006·American Journal of Respiratory Cell and Molecular Biology·Julia K L WalkerDavid A Schwartz
Apr 29, 2014·FEBS Letters·Vladimir J N Bykov, Klas G Wiman
Aug 11, 2007·Journal of Molecular Graphics & Modelling·Pramod C Nair, M Elizabeth Sobhia
Jul 1, 2010·Journal of Cellular Physiology·Ricardo E PerezMaria Laura Avantaggiati
Mar 25, 2010·Chemical Biology & Drug Design·Christine KaiserDavid O Azorsa
Jan 24, 2003·Expert Opinion on Therapeutic Targets·Molly B Schmid
Jun 24, 2015·Journal of Molecular Graphics & Modelling·Wilson Maldonado-RojasYovani Marrero-Ponce
Sep 26, 2009·BMC Bioinformatics·Pavithra Shivakumar, Michael Krauthammer
Nov 20, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Subrata Pramanik, Kunal Roy
Apr 23, 2009·Molecular Oncology·Nicole ZacheVladimir J N Bykov
Jun 29, 2004·Seminars in Cancer Biology·Susan Haupt, Ygal Haupt
Aug 4, 2006·European Journal of Medicinal Chemistry·Sumit Deswal, Nilanjan Roy
Jan 26, 2010·Archiv der Pharmazie·João P S FernandesCarlos A Brandt
Apr 29, 2004·SAR and QSAR in Environmental Research·A R CunninghamH S Rosenkranz
May 13, 2010·Journal of Biomolecular Screening·Pradeep Kumar NaikOwasis Rizvi
Nov 7, 2019·3 Biotech·Baban S KolteRohan J Meshram
Aug 7, 2007·Journal of Enzyme Inhibition and Medicinal Chemistry·Narsingh SachanVithal M Kulkarni
Sep 22, 2018·ACS Combinatorial Science·Harbil BediagaHumbert González-Díaz

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