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

Boiling point:

519.6±60.0 °C(Predicted)

Density 

1.218±0.06 g/cm3(Predicted)

storage temp. 

Desiccate at +4°C

solubility 

25℃: DMSO

form 

Powder

pka

9.76±0.40(Predicted)

color 

Off-white to light yellow

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

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.

Uses

H-1152 is a membrane-permeable and selective ROCK inhibitor, with a Ki value of 1.6 nM, and an IC50 value of 12 nM for ROCK2.

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.

IC 50

ROCKII: 12 nM (IC₅₀); CaMKII: 0.18 μM (IC₅₀); PKG: 0.36 μM (IC₅₀); AuroraA: 0.745 μM (IC₅₀); PKA: 3.03 μM (IC₅₀); Src: 3.06 μM (IC₅₀); PKC: 5.68 μM (IC₅₀); Abl: 7.77 μM (IC₅₀); MKK4: 16.9 μM (IC₅₀); MLCK: 28.3 μM (IC₅₀); EGFR: 50 μM (IC₅₀); GSK3α: 60.7 μM (IC₅₀); AMPK: 100 μM (IC₅₀); P38α: 100 μM (IC₅₀)

References

[1] Tamura M, et al. Development of specific Rho-kinase inhibitors and their clinical application. Biochim Biophys Acta. 2005 Dec 30;1754(1-2):245-52. Epub 2005 Sep 12. DOI:10.1016/j.bbapap.2005.06.015
[2] Ikenoya M, et al. Inhibition of rho-kinase-induced myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation in human neuronal cells by H-1152, a novel and specific Rho-kinase inhibitor. J Neurochem. 2002 Apr;81(1):9-16. DOI:10.1046/j.1471-4159.2002.00801.x
[3] Lie M, et al. Accelerated neurite growth from spiral ganglion neurons exposed to the Rho kinase inhibitor H-1152. Neuroscience. 2010 Aug 25;169(2):855-62. DOI:10.1016/j.neuroscience.2010.05.020

(S)-(+)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLYNYL)SULFONYL]HOMOPIPERAZINE(451462-58-1)Related Product Information

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• FASUDIL