Mechanism of action of the unusually potent microtubule inhibitor cryptophycin 1

Panda, Dulal ; Himes, Richard H. ; Moore, Richard E. ; Wilson, Leslie ; Jordan, Mary Ann (1997) Mechanism of action of the unusually potent microtubule inhibitor cryptophycin 1 Biochemistry, 36 (42). pp. 12948-12953. ISSN 0006-2960

Full text not available from this repository.

Official URL:

Related URL:


Cryptophycin 1 is a remarkably potent antiproliferative compound that shows excellent antitumor activity against mammary, colon, and pancreatic adenocarcinomas in mouse xenographs. At picomolar concentrations, cryptophycin 1 blocks cells in the G2/M phase of the cell cycle by an apparent action on microtubules. The compound binds to tubulin, inhibits microtubule polymerization, and depolymerizes preformed microtubules in vitro. Its exceptionally powerful antitumor activity (many-fold greater than paclitaxel or the vinca alkaloids) raises important questions about its mechanism of action. By quantitative video microscopy, we examined the effects of cryptophycin 1 on the dynamics of individual microtubules assembled to steady state from bovine brain tubulin. At low nanomolar concentrations, in the absence of net microtubule depolymerization, cryptophycin 1 potently stabilized microtubule dynamics. It reduced the rate and extent of microtubule shortening and growing and increased the frequency of rescue. The results suggest that cryptophycin 1 exerts its antiproliferative and antimitotic activity by binding reversibly and with high affinity to the ends of microtubules, perhaps in the form of a tubulin-cryptophycin 1 complex, resulting in the most potent suppression of microtubule dynamics yet described.

Item Type:Article
Source:Copyright of this article belongs to American Chemical Society.
ID Code:34901
Deposited On:14 Apr 2011 13:43
Last Modified:14 Apr 2011 13:43

Repository Staff Only: item control page