A tale of two tumor targets: topoisomerase I and tubulin. The Wall and Wani contribution to cancer chemotherapy.
The seminal discoveries of camptothecin and Taxol by Wall and Wani are discussed in a manner that demonstrates the influence that these two compounds has had on the further development of natural product, natural product-derived, and (some) synthetic entities as potential drug leads that interact either with tubulin or with topoisomerase I. The major categories of tubulin interactive agents in terms of inhibition and promotion of tubulin polymerization are briefly discussed. Likewise, a brief discussion of topoisomerase I inhibitors is presented. Lists of tubulin interactive agents and topoisomerase I inhibitors in preclinical and clinical development are given in Tables 2 and 3, respectively. This review is not meant to be exhaustive, but does illustrate the profound impact that these two plant-derived agents have had on cancer chemotherapy.
Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland 20892, USA. craggg@nail.nih.gov
Gordon M
GM
Cragg
David J
DJ
Newman
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D001685:Biological Factors / Q000737:chemistry* / Q000494:pharmacology*; D002166:Camptothecin / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D059004:Topoisomerase I Inhibitors; D050257:Tubulin Modulators
D000972:Antineoplastic Agents, Phytogenic; D001685:Biological Factors; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D050257:Tubulin Modulators; D017239:Paclitaxel; D002166:Camptothecin