Category: James K. Chen

Small-Molecule Inhibitors Of The AAA+ Atpase Motor Cytoplasmic Dynein

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.

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