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Molecular and Biological Determinants of the Cytotoxic Actions of Camptothecins: Perspective for the Development of New Topoisomerase I Inhibitors
Author(s) -
KOHN KURT W.,
POMMIER YVES
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb07021.x
Subject(s) - camptothecin , topoisomerase , computational biology , anticancer drug , drug action , pharmacology , rational design , drug discovery , drug , biology , chemistry , bioinformatics , dna , biochemistry , genetics
A bstract : Camptothecin, originally discovered in 1957 as an antitumor activity in plant extracts, has recently become one of the most promising leads to new anticancer drugs. After lingering for many years, interest in camptothecin was revitalized in 1985 upon discovery of its specific action on topoisomerase I. Detailed elucidation of action mechanisms at the molecular, cellular, and pharmacologic levels has made camptothecin and its congeners perhaps the best understood among clinical anticancer drugs. Promising chemical variants of camptothecin, and recently other chemical categories of topoisomerase I‐targeted drugs, provide unusually rich opportunities for rational drug selection and design. This is made possible by current concepts based, for the most part, on a sound experimental foundation, which points the way towards optimally effective therapy.