CSB

Stanford School of Medicine

Chemical & Systems Biology

 
 

Small-molecule inhibitors of the AAA+ ATPase motor cytoplasmic dynein

Posted by CSB Admin on April 5, 2012

Researchers:

Ari J. Firestone, Joshua S. Weinger, Maria Maldonado, Kari Barlan, Lance. D. Langston, Michael D. O’Donnell, Vladimir I. Gelfand, Tarun M. Kapoor, and James K. Chen

Summary:

The AAA+ ATPase motor cytoplasmic dynein regulates a diverse range of cellular functions, including mitotic spindle assembly, organelle trafficking, and ciliary and axonal transport. Since the dynamics of these processes are much faster than the action of reverse-genetic technologies, small-molecule modulators are essential tools for studying dynein-dependent biology. In the Apr. 5 issue of Nature, Firestone et al. reports the first chemical inhibitors of this minus-end-directed microtubule motor, which emerged from a high-throughput screen for Hedgehog pathway inhibitors. The benzoyl dihydroquinazolinone derivatives, collectively named “ciliobrevins” for their effects on primary cilia length, selectively inhibit cytoplasmic dynein 1 and 2, as demonstrated by their cellular phenotypes and actions on dynein function in vitro.