RKI-1447

RKI-1447 is a potent small molecule inhibitor of ROCK1 and ROCK2 with IC₅₀ values of 14.5 nM and 6.2 nM, respectively. IC50 & Target:IC50: 14.5 nM (ROCK1), 6.2 nM(ROCK2)^[1] In Vitro:RKI-1447 is a Type I kinase inhibitor that binds the ATP binding site through interactions with the hinge region and the DFG motif. RKI-1447 suppresses phosphorylation of the ROCK substrates mLC-2 and MYPT-1 in human cancer cells, but has no effect on the phosphorylation levels of the AKT, MEK and S6 kinase at concentrations as high as 10 μM. RKI-1447 is also highly selective at inhibiting ROCK-mediated cytoskeleton re-organization. RKI-1447 inhibits migration, invasion and anchorage-independent tumor growth of breast cancer cells^[1]. In Vivo:RKI-1447 is highly effective at inhibiting the outgrowth of mammary tumors in a transgenic mouse model. RKI-1447 inhibits mammary tumor growth by 87% and on average the mammary tumors from RKI-1447 treated mice are 7.7 fold smaller compared to those tumors from mice treated with the vehicle control^[1].