Camptothecin and taxol: from discovery to clinic.
Camptothecin (CPT) and taxol are secondary metabolites found in the stembark of Camptotheca acuminata, a native of China, and Taxus brevifolia, found in the northwest Pacific coastal region of the USA, respectively. The compounds were isolated through bioassay-guided fractionation of various extracts and through chromatographic fractions. Their unique and hitherto unknown structures were elucidated by nuclear magnetic resonance, mass spectrometry and X-ray analysis. Both compounds have unique mechanisms of antitumor activity; CPT uniquely inhibits an enzyme, topoisomerase I, involved in DNA replication, while taxol binds to a protein, tubulin, thus inhibiting cell division. Taxol has been called the best new anticancer agent developed from natural products, showing particular efficacy against ovarian cancer. CPT and analogs singly or combined with cisplatinum show efficacy against solid tumors, breast, lung, and colorectal, which hitherto have been unaffected by most cancer chemotherapeutic agents.
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Research Triangle Institute, Research Triangle Park, NC 27709-2194, USA.
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D000972:Antineoplastic Agents, Phytogenic / Q000266:history / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002166:Camptothecin / Q000266:history / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D056246:Chemistry, Analytic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002986:Clinical Trials as Topic; D003377:Countercurrent Distribution; D004791:Enzyme Inhibitors / Q000266:history / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D049673:History, 20th Century; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000266:history / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D050257:Tubulin Modulators; D014481:United States
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D050257:Tubulin Modulators; D017239:Paclitaxel; D002166:Camptothecin