Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle.
Tubulin is the biochemical target for several clinically used anticancer drugs, including paclitaxel and the vinca alkaloids vincristine and vinblastine. This review describes both the natural and synthetic agents which are known to interact with tubulin. Syntheses of the more complex agents are referenced and the potential clinical use of the compounds is discussed. This review describes the biochemistry of tubulin, microtubules, and the mitotic spindle. The agents are discussed in relation to the type of binding site on the protein with which they interact. These are the colchicine, vinca alkaloid, rhizoxin/maytansine, and tubulin sulfhydryl binding sites. Also included are the agents which either bind at other sites or unknown sites on tubulin. The literature is reviewed up to October 1997.
Jordan
A
A
Department of Chemistry, University of Manchester Institute of Science and Technology, UK.
Hadfield
J A
JA
Lawrence
N J
NJ
McGown
A T
AT
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001665:Binding Sites; D003078:Colchicine / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D008453:Maytansine / Q000494:pharmacology; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology; D011485:Protein Binding; D008941:Spindle Apparatus / Q000737:chemistry / Q000187:drug effects*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects; D050257:Tubulin Modulators; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D018942:Macrolides; D013439:Sulfhydryl Reagents; D014404:Tubulin; D050257:Tubulin Modulators; D008453:Maytansine; D014750:Vincristine; D014747:Vinblastine; C041443:rhizoxin; D017239:Paclitaxel; D003078:Colchicine