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Camptothecin and taxol – from nature to bench to bedside
Camptothecin (CPT) and taxol are secondary metabolites found, respectively, in the wood bark of Camptotheca acuminata, a native of China, and Taxus brevifolia, found in the Pacific north-west coastal region of the USA. The compounds were isolated by the bioassay-guided fractionation of the crude plant material and their structures established by single crystal X-ray analysis. Both compounds have unique mechanisms of antitumour activity. Camptothecin inhibits an enzyme, topoisomerase I, involved in DNA replication. Taxol binds to a protein, tubulin, thus inhibiting cell division. Currently, two analogues of camptothecin, topotecan (Hycamtin®, GlaxoSmithKline, Brentford, UK) and irinotecan (Campto®, Pfizer Ltd, New York, NY, USA), and taxol and its analogues, docetaxel (Taxotere®, Sanofi-Aventis Ltd, Guilford, UK) and cabazitaxel (Jevtana®, Sanofi-Aventis Ltd, Guilford, UK), are approved for clinical use in the USA by the Food and Drug Administration (FDA).
The camptothecin analogues are used to treat ovarian, colorectal and small-cell lung cancers. Taxol is used extensively to treat refractory ovarian, breast and non-small-cell lung cancers and Kaposi’s sarcoma. Docetaxel has been a very important drug for the treatment of breast cancer and cabazitaxel is FDA approved for the treatment of hormone-refractory prostate cancer.