Evaluated: UA62784 Is a cytotoxic inhibitor of microtubules, not CENP-E.

This paper recently caught my eye. I evaluated it for Faculty of 1000.

S Tcherniuk,S Deshayes,V Sarli,G Divita,A Abrieu (2011)
UA62784 Is a cytotoxic inhibitor of microtubules, not CENP-E.
Chem Biol 18, 5.
PMID: 21609844 DOI: 10.1016/j.chembiol.2011.03.006

F1000 evaluation at: http://f1000.com/14267299

This paper caught my eye as it alters our perception of the target of the small molecule inhibitor UA62784. Previously characterised as a CENP-E inhibitor, the authors here show that it is in fact a potent inhibitor of microtubule dynamics and has no inhibitory effect on CENP-E in vitro.

While clearly of interest to those in the mitosis field, this work also has great importance for those (including us) who have used such compounds for other reasons. It also provides a nice chemical biology story relating to the importance of target validation. Indeed, there are two companion pieces relating to this issue that I would also recommend reading {1,2}.


{1} Chemical inhibitors: the challenge of finding the right target.
Calligaris D, Lafitte D
Chemistry & Biology 2011 May 27; 18(5): 555-7

{2} Motor-dependent and -independent roles of CENP-E at kinetochores: the cautionary tale of UA62784.
Maiato H, Logarinho E
Chemistry & Biology 2011 Jun 24; 18(6): 679-80