Microtubule-stabilizing natural products as promising cancer therapeutics.
Paclitaxel and related taxanes exhibit their anticancer activity by promoting tubulin polymerization and stabilizing microtubules, which results in mitotic G2/M arrest and apoptosis. The clinical success of paclitaxel in treating a wide array of tumor types has led to numerous efforts to identify novel natural products with paclitaxel-like mechanisms of action, but which may overcome some of the liabilities of the taxanes. Although the list of natural products that share the paclitaxel-like mechanism is relatively small, it continues to expand and currently includes a number of structurally distinct classes. Despite the mechanistic similarities between these classes, differences exist which may translate into their differential efficacy in the clinic. The past several years have seen a considerable amount of pre-clinical and clinical progress in developing these novel microtubule-stabilizing natural products as cancer therapeutics. This review focuses primarily on recent advances published since 2002.
Gallagher
Brian M
BM
Alantos Pharmaceuticals, Inc., Cambridge, MA 02139, USA. bmgallagherjr@hotmail.com
D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy*; D014404:Tubulin / Q000378:metabolism
D001688:Biological Products; D014404:Tubulin