Motor cytoplasmic dynein is an ATPase that regulates ciliary trafficking, mitotic spindle formation and organelle transport. Firestone et al. described the discovery of the first specific small-molecule antagonists of cytoplasmic dynein, termed ciliobrevins. They showed that ciliobrevins modulate protein trafficking within primary cilia, which leads to blockade of Hedgehog signalling (a pathway that is implicated in cancer). Moreover, the compounds blocked dynein-dependent microtubule gliding and ATPase activity, and so could be useful tool compounds for studying cellular processes and for stimulating the development of further ciliobrevin-like inhibitors.
ORIGINAL RESEARCH PAPER
Firestone, A. J. et al. Small-molecule inhibitors of the AAA+ ATPase motor cytoplasmic dynein. Nature 484, 125–129 (2012)
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Harrison, C. Small-molecule inhibitors of cytoplasmic dynein. Nat Rev Drug Discov 11, 354 (2012). https://doi.org/10.1038/nrd3740
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DOI: https://doi.org/10.1038/nrd3740