H-1152

H-1152, an isoquinolinesulfonamide derivative, is a potent, selective and membrane-permeable inhibitor of Rho-kinase with a Ki value of 1.6 nM, revealing a high selectivity over other serine/threonine kinases.
In human neuroteratoma (NT-2) cells, H-1152 has shown to dose-dependently block lysophosphatidic acid (LPA)-induced myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation with an IC50 value of 2.5 μM [1].
Human trabecular meshwork (HTM) cells treated with H-1152 has been revealed cell elongation and separation, deterioration, focal adhesions, and loss of actin stress fibers. Rat eyes treated with H-1152 has been demonstrated a remarkable decrease in intraocular pressure (IOP) and an expansion of the intracellular spaces and loss of extracellular material in the juxtacanalicular region of the TM [2].
H-1152 has been revealed to increase population of neurite lengths in dissociated cultures of postnatal mouse spiral ganglia.However, H1152 has shown to have no effect on reducing alterations in different neuronal morphologies ratios or neuronal survival [3].
H-1152 has shown to lead to rightward shifts in the curves to phenylephrine (PE) with no significant effect on the electrical field stimulation (EFS) induced contractions. In addition, H-1152 at 100 nmol/kg administrated intraperitoneally has been revealed to remarkably increase cavernous nerve stimulation induced erectile responses [4]
References:
1.Ikenoya M1, Hidaka H, Hosoya T, Suzuki M, Yamamoto N, Sasaki Y. 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.Yu M1, Chen X, Wang N, Cai S, Li N, Qiu J, Brandt CR, Kaufman PL, Liu X.
H-1152 effects on intraocular pressure and trabecular meshwork morphology of rat eyes. J Ocul Pharmacol Ther. 2008 Aug;24(4):373-9. doi: 10.1089/jop.2008.0029.
3.Lie M1, Grover M, Whitlon DS. 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. Epub 2010 May 15.
4.Teixeira CE1, Ying Z, Webb RC. 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. Epub 2005 Jun 23.