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LIM kinase (LIMK) inhibitors target LIMK1 and LIMK2, two protein kinases that regulate actin filaments. The LIM name comes from a zinc-binding domain first found in the proteins Lin-11, Isl-1 and Mec-3. In 1998 two groups showed that LIMK1 phosphorylates cofilin and so inactivates this actin-depolymerizing factor. Phosphorylated cofilin no longer severs filaments, and filamentous actin accumulates. Upstream, Rho-associated protein kinase (ROCK) activates LIMK1 by phosphorylating threonine 508 in its activation loop. LIMK inhibitors are used to study cell migration, invasion and neuronal morphology. BMS-5 and BMS-3 inhibit both isoforms, while T56-LIMKi and LX7101 are listed as LIMK2 inhibitors. TH-257 and TH-263 are further LIMK inhibitors listed in this category.
