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Rho-associated kinase (ROCK), an effector of the small GTP-binding protein Rho, plays an important role in various cellular functions including vascular smooth muscle contraction, proliferation, and migration as well as inflammatory cell mobility. HA-1077 is a potent inhibitor of ROCK-II and additionally inhibits protein kinase c-related kinase 2 (PRK2), mitogen- and stress-activated protein kinase (MSK1), and mitogen activated protein kinase-activated protein kinase 1b (MAPKAP-K1b) with IC50 values of 1.9, 4, 5, and 15 µM, respectively. By inhibiting the activity of ROCK, HA-1077 has been shown to reduce blood vessel constriction, decrease pulmonary arterial pressure, inhibit tumor angiogenesis, and improve insulin signaling in various rodent models. While originally marketed for the prevention of cerebral vasospasm in patients with subarachnoid hemorrhage, oral formulations of HA-1077 are used for the treatment of a wide range of cardiovascular diseases including pulmonary arterial hypertension and stable angina.

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