TC-S 7001 is an inhibitor of Rho-associated kinase (ROCK; IC50s = 0.6 and 1.1 nM, respectively, for human ROCK1 and ROCK2).1 It is selective for ROCK over myosin light-chain kinase (MLCK) and zipper-interacting protein kinase (ZIP-kinase; IC50s = 7,400 and 4,100 nM, respectively), as well as 110 kinases in a panel at 1-10 ?M, but does inhibit TRK and FLT3 (IC50s = 252 and 303 nM, respectively). TC-S 7001 reduces ROCK2-induced phosphorylation of human myosin-binding subunit (MBS) when used at a concentration of 3 nM and decreases ROCK2 autophosphorylation. It inhibits contraction of isolated rabbit saphenous artery induced by phenylephrine (IC50 = 65 nM) and decreases blood pressure in normotensive and hypertensive rats when administered at doses of 3 and 10 mg/kg. TC-S 7001 also decreases right ventricular systolic pressure and total pulmonary resistance in a rat model of monocrotaline-induced pulmonary hypertension when administered at a dose of 10 mg/kg per day.2
1.Kast, R., Schirok, H., Figueroa-Pérez, S., et al.Cardiovascular effects of a novel potent and highly selective azaindole-based inhibitor of Rho-kinaseBr. J. Pharmacol.152(7)1070-1080(2007) 2.Dahal, B.K., Kosanovic, D., Pamarthi, P.K., et al.Therapeutic efficacy of azaindole-1 in experimental pulmonary hypertensionEur. Respir. J.36(4)808-818(2010)