H-1152Rho-kinase inhibitor CAS# 451462-58-1 |
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Quality Control & MSDS
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| Cas No. | 451462-58-1 | SDF | Download SDF |
| PubChem ID | 448043 | Appearance | Powder |
| Formula | C16H21N3O2S | M.Wt | 319.42 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | 25℃: DMSO | ||
| Chemical Name | 4-methyl-5-[[(2S)-2-methyl-1,4-diazepan-1-yl]sulfonyl]isoquinoline | ||
| SMILES | CC1CNCCCN1S(=O)(=O)C2=CC=CC3=CN=CC(=C32)C | ||
| Standard InChIKey | AWDORCFLUJZUQS-ZDUSSCGKSA-N | ||
| Standard InChI | InChI=1S/C16H21N3O2S/c1-12-9-18-11-14-5-3-6-15(16(12)14)22(20,21)19-8-4-7-17-10-13(19)2/h3,5-6,9,11,13,17H,4,7-8,10H2,1-2H3/t13-/m0/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | 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.In Vitro:H-1152 is an inhibitor of Rho-kinase, with an IC50 of 12 nM for ROCK2. H-1152 (H-1152P) also shows less inhibitory activities against CaMKII, PKG, AuroraA, PKA, Src, PKC, MLCK, Abl, EGFR, MKK4, GSK3α, AMPK, and P38α, with IC50s of 0.180, 0.360, 0.745, 3.03, 3.06, 5.68, 28.3, 7.77, 50.0, 16.9, 60.7, 100, and 100 μM, respectively[1]. H-1152 potently inhibits Rho kinase, with a Ki of 1.6 nM, and slightly suppresses PKA, PKC and MLCK, with Kis of 0.63, 9.27, and 10.1 μM, respectively. H-1152 (0.1-10 µM) highly inhibits MARCKS phosphorylation, with an IC50 value of 2.5 µM in LPA-treated cells, but shows no such obvious effects in PDBu-treated cells[2]. H-1152 (0.5-10 μM) cuases no decreased neuronal survival. H-1152 (1, 5 or 10 μM) also exerts no alterations in the ratios of different neuronal morphologies. Furthermore, H-1152 (10 μM) increases neurite length in both BMP4 and LIF cultures[3]. References: | |||||
H-1152 Dilution Calculator
H-1152 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 3.1307 mL | 15.6534 mL | 31.3067 mL | 62.6135 mL | 78.2669 mL |
| 5 mM | 0.6261 mL | 3.1307 mL | 6.2613 mL | 12.5227 mL | 15.6534 mL |
| 10 mM | 0.3131 mL | 1.5653 mL | 3.1307 mL | 6.2613 mL | 7.8267 mL |
| 50 mM | 0.0626 mL | 0.3131 mL | 0.6261 mL | 1.2523 mL | 1.5653 mL |
| 100 mM | 0.0313 mL | 0.1565 mL | 0.3131 mL | 0.6261 mL | 0.7827 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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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.
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Proerectile effects of the Rho-kinase inhibitor (S)-(+)-2-methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl]homopiperazine (H-1152) in the rat penis.[Pubmed:15976017]
J Pharmacol Exp Ther. 2005 Oct;315(1):155-62.
The Rho-kinase pathway mediates Ca2+ sensitization in the penile circulation, which maintains the penis in the flaccid state. We aimed to investigate the functional effect of a novel Rho-kinase inhibitor, H-1152 [(S)-(+)-2-methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl]homopiperazine], both in vitro and in vivo as well as to demonstrate the expression of Rho guanine nucleotide exchange factors (RhoGEFs) in the rat corpus cavernosum (CC), by using a semiquantitative reverse transcription-polymerase chain reaction assay to measure their mRNA expression. 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). It is noteworthy that when H-1152 or Y-27632 was combined with SNP, a marked synergistic inhibition was noted both on PE- and EFS-induced contractions. Intraperitoneal administration of H-1152 (100 nmol/kg) had a discrete effect on mean arterial pressure and significantly enhanced erectile responses evoked by stimulation of the cavernous nerve. The mRNA expression for PDZ-RhoGEF, p115RhoGEF, and leukemia-associated RhoGEF in cavernosal segments was visualized by electrophoresis on agarose gel. The results indicate that H-1152 is a powerful Rho-kinase inhibitor, giving rise to its therapeutic potential in the treatment of erectile dysfunction. The regulator of G-protein signaling-containing RhoGEFs may represent key components of the molecular mechanisms associated with the abnormal function of the cavernosal smooth muscle.
H-1152 effects on intraocular pressure and trabecular meshwork morphology of rat eyes.[Pubmed:18665808]
J Ocul Pharmacol Ther. 2008 Aug;24(4):373-9.
PURPOSE: The aim of this study was to elucidate the effects of the Rho-kinase inhibitor, H-1152, on cultured human trabecular meshwork (HTM) cells, TM morphology, and intraocular pressure (IOP) in rats. METHODS: Cultured HTM cells were treated with H-1152. Changes in cell morphology and the organization of the actin cytoskeleton and focal adhesions were evaluated by microscopy and immunofluorescence. H-1152 was administered topically to the eyes of conscious rats, and IOP was measured with a commercially available tonometer before and after treatment. The eyes were enucleated 1 h after treatment, fixed, and processed for morphologic analysis by light and electron microscopy. RESULTS: Exposure of the cultured HTM cells to 20 microM of H-1152 induced elongation and separation of cells, deterioration, and loss of actin stress fibers and focal adhesions within 2 h. 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. CONCLUSIONS: The IOP-lowering effect of H-1152 in rat eyes is likely due to changes in TM-cell morphology, the actin cytoskeleton, and cellular adhesions in the conventional outflow pathway. H-1152 has potential as a new antiglaucoma medication.
Accelerated neurite growth from spiral ganglion neurons exposed to the Rho kinase inhibitor H-1152.[Pubmed:20478368]
Neuroscience. 2010 Aug 25;169(2):855-62.
Upon the death of their hair cell synaptic partners, bipolar cochlear spiral ganglion neurons either die or retract their peripheral nerve fibers. Efforts to induce the regrowth of the peripheral neurites have had to rely on limited knowledge of the mechanisms underlying spiral ganglion neurite regeneration and have been restricted by the impracticality of undertaking large numbers of manual analyses of neurite growth responses. Here we have used dissociated cultures of postnatal mouse spiral ganglia to assess the effects of the Rho kinase inhibitor H-1152 on neurite growth and to determine the utility of automated high content analysis for evaluating neurite length from spiral ganglion neurons in vitro. In cultures of postnatal mouse spiral ganglion, greater than 95% of the neurons develop bipolar, monopolar or neurite-free morphologies in ratios dependent on whether the initial medium composition contains leukemia inhibitory factor or bone morphogenetic protein 4. Cultures under both conditions were maintained for 24 h, then exposed for 18 h to H-1152. None of the cultures exposed to H-1152 showed decreased neuronal survival or alterations in the ratios of different neuronal morphologies. However, as measured manually, the population of neurite lengths was increased in the presence of H-1152 in both types of cultures. High content analysis using the Arrayscan VTi imager and Cellomics software confirmed the rank order differences in neurite lengths among culture conditions. These data suggest the presence of an inhibitory regulatory mechanism(s) in the signaling pathway of Rho kinase that slows the growth of spiral ganglion neurites. The automated analysis demonstrates the feasibility of using primary cultures of dissociated mouse spiral ganglion for large scale screens of chemicals, genes or other factors that regulate neurite growth.
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.[Pubmed:12067241]
J Neurochem. 2002 Apr;81(1):9-16.
The functions of small G protein Rho-associated kinase (Rho-kinase) have been determined in muscle and non-muscle cells, but, particularly in neuronal cells, its effector(s) has not been well known. Recently, we preliminarily reported that Rho-kinase phosphorylates the Ser159 residue in myristoylated alanine-rich C kinase substrate (MARCKS) in vitro, but it remains obscure in vivo. To further clarify this point, we developed an isoquinolinesulfonamide derivative, H-1152, that 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. 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). In contrast, two other Rho-kinase inhibitors, HA-1077 at 30 microM and Y-27632 at 10-30 microM, inhibited the phosphorylation of MARCKS in the cells stimulated by LPA and PDBu. A PKC inhibitor Ro-31-8220 selectively inhibited PDBu-induced phosphorylation of MARCKS. Taken together with our previous results, the present findings strongly suggest that Rho/Rho-kinase phosphorylates MARCKS at Ser159 residue in neuronal cells in response to LPA stimulation and that H-1152 is a useful tool to confirm Rho-kinase function(s) in cells and tissues.
