Camptothecin and taxol: discovery to clinic.
Camptothecin (CPT) is a pentacyclic alkaloid isolated from wood and bark of Camptotheca acuminata. Initially it was found to be highly active in a number of mouse in vivo cancer assays. Subsequently, CPT was found to uniquely inhibit an enzyme, topoisomerase I, which is involved in DNA replication. A number of CPT analogs are in advanced clinical trial, and two, Topotecan and CPT-11, have been approved for marketing by the FDA. taxol, a taxane alkaloid, was isolated from Taxus brevifolia. Taxol is a highly cytotoxic compound active in several mouse antitumor assays. It was subsequently found to uniquely inhibit tubulin, a protein involved in mitosis. After clinical evaluation, it has become the drug of choice for treatment of ovarian cancer.
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Research Triangle Institute, Research Triangle Park, NC 27709-2194, USA.
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002166:Camptothecin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002986:Clinical Trials as Topic; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D017239:Paclitaxel / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010944:Plants / Q000737:chemistry; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D002166:Camptothecin