Taccalonolides: Novel microtubule stabilizers with clinical potential.
Nature remains an important source for new anticancer drugs. Numerous microtubule-targeting agents currently approved or in clinical development, including paclitaxel, vinblastine, vincristine, colchicine and combretastatin, are plant-derived compounds. The microtubule stabilizing properties of the taccalonolides were discovered as a part of a program to identify new microtubule stabilizers from natural sources. The taccalonolides are unique among all other agents in this class in that they stabilize microtubules through a mechanism of action that does not involve direct tubulin binding. Herein we review the discovery and isolation of the taccalonolides, their biological activities in vitro and in vivo and their potential advantages over clinically used microtubule stabilizers. We also discuss the challenges in formulation and supply that will need to be solved before the taccalonolides can become candidates for clinical development.
Risinger
April L
AL
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 78229, United States.
Mooberry
Susan L
SL
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D013256:Steroids / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D013256:Steroids; D050257:Tubulin Modulators; C475870:taccalonolide A; C475869:taccalonolide E