H-1152 dihydrochloride

• CAT Number: I005249
• CAS Number: 871543-07-6
• Molecular Formula: C16H23Cl2N3O2S
• Molecular Weight: 392.34
• Purity: ≥95%
• Synonyms: 4-methyl-5-((2-methyl-1,4-diazepan-1-yl)sulfonyl)isoquinoline dihydrochloride
• Target: TGF-beta/Smad
• Solubility: DMSO: ≥ 32 mg/mL
• Storage: Store at -20°C
• IC50: 1.6 nM (Ki Value) [1]

H-1152 2Hcl, an isoquinolinesulfonamide derivative, is a more specific, stronger and membrane-permeable inhibitor of Rho-kinase with a Ki value of 1.6 nM, but poor inhibitor of other serine/threonine kinases.IC50 Value: 1.6 nM (Ki Value) [1]Target: ROCKin vitro: H-1152 dose-dependently inhibited the phosphorylation of MARCKS in human neuroteratoma (NT-2) cells stimulated by Rho-activator lysophosphatidic acid (LPA), which was determined by phosphorylation site-specific antibody against phospho-Ser159 in MARCKS, whereas it hardly inhibited the phosphorylation stimulated by phorbol-12,13-dibutyrate (PDBu) [1]. Loss-of-function experiments in endothelial cells revealed that inhibition of ROCK I/II using the pharmacological inhibitor H-1152 and ROCK I/II-specific small-interfering RNAs resulted in a rise of VEGF-driven sprouting angiogenesis [3].in vivo: Cumulative addition of H-1152 (0.001-3 microM) or Y-27632 [0.01-30 microM; (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide] caused sustained relaxations of precontracted CC strips, which were not affected by inhibition of the nitric oxide signaling pathway. Addition of H-1152 (0.1 microM), Y-27632 (1 microM), or sodium nitroprusside (SNP; 0.1 microM) caused rightward shifts in the curves to phenylephrine (PE), but it had little effect on the contractions mediated by electrical field stimulation (EFS) [2]. Topical administration of H-1152 resulted in a significant decrease in IOP from 0.5 to 6 h, with the maximum IOP reduction of 28.1% at 1 h post-treatment (P < 0.001; n = 10). H-1152 caused an expansion of the intercellular spaces and loss of extracellular material in the juxtacanalicular region of the TM in rat eyes [4].

Reference

[1]. 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.
[2]. Teixeira CE, et al. Proerectile effects of the Rho-kinase inhibitor (S)-(+)-2-methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl]homopiperazine (H-1152) in the rat penis. J Pharmacol Exp Ther. 2005 Oct;315(1):155-62.
[3]. Kroll J, et al. Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven retinal neovascularization and sprouting angiogenesis. Am J Physiol Heart Circ Physiol. 2009 Mar;296(3):H893-9.
[4]. Yu M, et al. H-1152 effects on intraocular pressure and trabecular meshwork morphology of rat eyes. J Ocul Pharmacol Ther. 2008 Aug;24(4):373-9.