(S)-(+)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLYNYL)SULFONYL]HOMOPIPERAZINE

Description

Rho-associated kinase (ROCK), activated by GTP-linked Rho, phosphorylates targets that are involved in cytoskeletal remodeling, smooth muscle contraction, and neuronal development. H-1152 is a potent, specific, ATP-competitive, and cell permeable inhibitor of ROCK (K_i = 1.6 nM). It is a more potent inhibitor of ROCK than either Y-27632 (K_i = 140 nM) or HA-1077 (K_i = 330 nM). H-1152 poorly inhibits PKA, PKC, and myosin light chain kinase (K_i = 0.63, 9.27, and 10.1 μM, respectively). It has been used to examine the role of ROCK in such diverse processes as stress fiber assembly, vasoconstriction, as well as spontaneously tonic smooth muscle and neurite extension.

Definition

ChEBI: (S)-2-methyl-1-(4-methylisoquinoline-5-sulfonyl)-1,4-diazepane is a member of the class of isoquinolines that is the sulfonamide formed by the formal condensation of the sulfo group of 4-methylisoquinoline-5-sulfonic acid with the 1-amino group of (S)-2-methyl-1,4-diazepane. It has a role as an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor. It is a member of isoquinolines and a N-sulfonyldiazepane. It is a conjugate base of a (S)-2-methyl-1-(4-methylisoquinoline-5-sulfonyl)-1,4-diazepane(2+).

Biological Activity

Rho-kinase (ROCK) inhibitor that displays high selectivity over other protein kinases (IC 50 values are 0.012, 0.180, 0.360, 0.745, 3.03, 5.68 and 28.3 μ M for ROCKII, CAMKII, PKG, Aurora A, PKA, PKC and MLCK respectively). Inhibits sulprostone-induced contractions in guinea pig aorta (IC 50 = 190 nM) and displays proerectile effects in rats.