1-(5-Isoquinolinylsulfonyl)homopiperazine dihydrochloride, Fasudil dihydrochloride

Description

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 ROCK2 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.

Chemical Properties

White fine crystalline powder

Uses

HA-1077 dihydrochloride has been used:

• to relax cantilevers
• in the functional assessment of isolated coronary arteries
• to investigate the effect of azaindole-1, fasudil on acute hypoxic pulmonary vasoconstriction (HPV)

Uses

Fasudil dihydrochloride is used in the inhibition of contractile responses to potassium chloride, phenylephnne (PHE), prostaglandin and hepatic stellate cells spreading. It is also used in the formation of stress fibers and in medicine.

Biochem/physiol Actions

Novel vasodilator agent which inhibits vascular smooth muscle contraction by acting as an intracellular Ca2+ antagonist.