Small-molecule inhibitors of dynein motor proteins

Stanford and Rockefeller researchers have identified and developed dynein-specific inhibitors that have significant medical applications involving mitotic spindle assembly, organelle transport, and primary cilia formation. The quinazolinones and structural analogs may be utilized as selective anti-mitotic cancer therapies, as they concurrently target cytoplasmic dynein-dependent primary cilia function, which would lead to the blockade of cilia-regulated processes such as oncogenic Hedgehog pathway activation. Though not confirmed of their effectiveness on axonemal dyneins, inhibitors of this dynein subfamily could in principle block movement of motile cilia and flagella, which could have significant implications for sperm immobilization, and the pharmacological modeling of human ciliopathies such as polycystic kidney disease, Baret-Biedl syndrome, Meckel-Gruber syndrome, and retinal degeneration.