Background:

RKI-1447 is a potent inhibitor of ROCK 1 and 2 (Rho-associated protein kinase 1 and 2).

ROCK is a serine-threonine kinase, which regulates cell shape and movement via acting on cytoskeleton.

RKI-1447 specifically and dose-dependently inhibits ROCK1 and ROCK2. RKI-1447 inhibited the phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells. However, it does not affect the phosphorylation of the AKT, MEK, and S6 kinase at a high concentrations of 10 μmol/L. It indicated a high specificity. Additionally, it was also observed that RKI-1447 selectively suppressed ROCK-mediated cytoskeleton re-organization following LPA stimulation, but does not affect PAK-meditated lamellipodia and filopodia formation following PDGF and Bradykinin stimulation. RKI-1447 inhibited migration, invasion and anchorage-independent tumor growth of breast cancer cells [1]

In mouse model, tumors were monitored at the time of tumor onset and the beginning of treatment (once a day for 14 days) with vehicle (20% HPCD) or RKI-1447 (200 mg/kg/day), when tumor volumes reached 75 to 2,300 mm3. Tumors from mice treated with vehicle increased in average tumor volume of 68.3% but tumors from mice treated with the RKI-1447 increased in average tumor volume of only 8.8%. Thus, RKI-1447 inhibited mammary tumor growth by 87% [1].

Reference:
[1] Patel R A et al. , RKI-1447 Is a Potent Inhibitor of the Rho-Associated ROCK Kinases with Anti-Invasive and Antitumor Activities in Breast Cancer. Cancer Res, 2012, 72(19): 5025-5034.