Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C14H21N3O |
Molecular Weight | 247.336 |
Optical Activity | ( + ) |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@@H](N)[C@H]1CC[C@@H](CC1)C(=O)NC2=CC=NC=C2
InChI
InChIKey=IYOZTVGMEWJPKR-IJLUTSLNSA-N
InChI=1S/C14H21N3O/c1-10(15)11-2-4-12(5-3-11)14(18)17-13-6-8-16-9-7-13/h6-12H,2-5,15H2,1H3,(H,16,17,18)/t10-,11-,12-/m1/s1
Molecular Formula | C14H21N3O |
Molecular Weight | 247.336 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Y-27632, originally synthesized by Mitsubishi Tanabe Pharma Corporation, is a selective and a strong ROCK inhibitor, which activates the ROCK signal cascade. It was found, that the inhibition of ROCK was beneficial for the prevention of systemic lupus erythematosus, which possibly by suppressing NF-κB activation. Y-27632 can promote both the ex vivo and in vitro proliferation of limbal epithelial cell proliferation. The in vivo enhanced epithelial wound healing further implies that the Y-27632 may act as a new strategy for treating limbal stem cell deficiency. Preliminary human cases confirmed that ROCK inhibitor eye drops were considered effective for treatment of corneal edema associated with cataract surgery.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Q13464 Gene ID: 6093.0 Gene Symbol: ROCK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9353125 |
0.22 µM [Ki] | ||
Target ID: O75116 Gene ID: 9475.0 Gene Symbol: ROCK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382 |
0.3 µM [Ki] | ||
Target ID: Q13464 Gene ID: 6093.0 Gene Symbol: ROCK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382 |
0.22 µM [IC50] | ||
Target ID: O75116 Gene ID: 9475.0 Gene Symbol: ROCK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382 |
0.3 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Preventing | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. | 1997 Oct 30 |
|
Y-27632 potentiates relaxant effects of beta 2-adrenoceptor agonists in bovine tracheal smooth muscle. | 2000 Feb 11 |
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Long-term effects of benidipine on cerebral vasoreactivity in hypertensive rats. | 2002 Mar 8 |
|
Involvement of Rho-kinase pathway for angiotensin II-induced plasminogen activator inhibitor-1 gene expression and cardiovascular remodeling in hypertensive rats. | 2002 May |
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Cerivastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, inhibits cardiac myocyte hypertrophy induced by endothelin. | 2002 Oct 25 |
|
Inhibitory effect of fluvastatin on lysophosphatidylcholine-induced nonselective cation current in Guinea pig ventricular myocytes. | 2002 Sep |
|
Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta. | 2003 Feb |
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Cardiovascular effects of Y-27632, a selective Rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model. | 2003 Jan 26 |
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Rho kinase mediates serum-induced contraction in fibroblast fibers independent of myosin LC20 phosphorylation. | 2003 Mar |
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Involvement of Rho-kinase in P2Y-receptor-mediated contraction of renal glomeruli. | 2003 Mar 21 |
|
Vanadate activates Rho A translocation in association with contracting effects in ileal longitudinal smooth muscle of guinea pig. | 2004 Aug |
|
Rho-kinase expression and its contribution to the control of perfusion pressure in the isolated rat mesenteric vascular bed. | 2004 Feb 6 |
|
8-Bromo-cAMP decreases the Ca2+ sensitivity of airway smooth muscle contraction through a mechanism distinct from inhibition of Rho-kinase. | 2004 Oct |
|
Upregulation of Rho-kinase (ROCK-2) expression and enhanced contraction to endothelin-1 in the mesenteric artery from lipopolysaccharide-treated rats. | 2004 Sep 13 |
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Key role of myosin light chain (MLC) kinase-mediated MLC2a phosphorylation in the alpha 1-adrenergic positive inotropic effect in human atrium. | 2005 Jan 1 |
|
Screening for cell migration inhibitors via automated microscopy reveals a Rho-kinase inhibitor. | 2005 Mar |
|
Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts. | 2005 Oct |
|
Thrombin-induced contraction in alveolar epithelial cells probed by traction microscopy. | 2006 Aug |
|
Roles of stretch-activated cation channel and Rho-kinase in the spontaneous contraction of airway smooth muscle. | 2006 Dec 15 |
|
M2 and M3 muscarinic receptor activation of urinary bladder contractile signal transduction. I. Normal rat bladder. | 2006 Feb |
|
Role of Rho-kinase in guinea-pig gallbladder smooth muscle contraction. | 2006 Mar 18 |
|
Beneficial effects of the Rho kinase inhibitor Y27632 in murine puromycin aminonucleoside nephrosis. | 2008 |
|
Nitric oxide does not downregulate Rho-kinase (ROCK-2) expression in rat coronary endothelial cells. | 2008 Feb |
|
Simvastatin inhibits central sympathetic outflow in heart failure by a nitric-oxide synthase mechanism. | 2008 Jul |
|
Inorganic arsenic activates reduced NADPH oxidase in human primary macrophages through a Rho kinase/p38 kinase pathway. | 2008 May 1 |
|
Dual pathway activated by tert-butyl hydroperoxide in human airway anion secretion. | 2008 Nov |
|
Effects of a selective Rho-kinase inhibitor Y-27632 on oxidative stress parameters in acute dichlorvos poisoning in rats. | 2008 Oct |
|
Calcium sensitization in human esophageal muscle: role for RhoA kinase in maintenance of lower esophageal sphincter tone. | 2008 Oct |
|
Combined inhibition of Cdk5 and ROCK additively increase cell survival, but not the regenerative response in regenerating retinal ganglion cells. | 2009 Dec |
|
Agonist-biased signaling via proteinase activated receptor-2: differential activation of calcium and mitogen-activated protein kinase pathways. | 2009 Oct |
|
Suppression of hepatitis C virus replication by protein kinase C-related kinase 2 inhibitors that block phosphorylation of viral RNA polymerase. | 2009 Oct |
|
Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. | 2009 Sep |
|
Statin's excitoprotection is mediated by sAPP and the subsequent attenuation of calpain-induced truncation events, likely via rho-ROCK signaling. | 2009 Sep 9 |
|
The suppressive effect of Rho kinase inhibitor, Y-27632, on oncogenic Ras/RhoA induced invasion/migration of human bladder cancer TSGH cells. | 2010 Jan 5 |
|
The protective effect of Rho-associated kinase inhibitor on aluminum-induced neurotoxicity in rat cortical neurons. | 2010 Jul |
|
Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account. | 2010 Jun 1 |
|
Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral neuropathy induced by anti-cancer drug cisplatin. | 2010 Mar |
|
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. | 2011 Oct 30 |
|
GEF-H1/RhoA signalling pathway mediates lipopolysaccharide-induced intercellular adhesion molecular-1 expression in endothelial cells via activation of p38 and NF-κB. | 2012 Mar |
|
Critical roles of Rho-associated kinase in membrane blebbing and mitochondrial pathway of apoptosis caused by 1-butanol. | 2012 Sep |
|
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. | 2013 Apr 15 |
|
Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy. | 2013 Apr 30 |
|
RhoGEF17, a Rho-specific guanine nucleotide exchange factor activated by phosphorylation via cyclic GMP-dependent kinase Iα. | 2013 Mar |
|
ROCK-dependent ATP5D modulation contributes to the protection of notoginsenoside NR1 against ischemia-reperfusion-induced myocardial injury. | 2014 Dec 15 |
|
The role of Rho-kinases in IL-1β release through phagocytosis of fibrous particles in human monocytes. | 2015 Jan |
Patents
Sample Use Guides
in patients: Y-27632 (10 mM), eye drops topically
in mice: 5mg/kg Y-27632 was intravenously injected
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382
Myc-tagged ROCK-I precipitated from lysates of HeLa cells overexpressing this kinase was incubated with 330 μg of protein/ml of histone type 2 and 1 μM ATP at 30°C. Recombinant ROCK-I was then incubated with various concentrations of ATP at 37°C for 30 min, and the enzyme kinetics was analyzed. This analysis revealed the Michaelis-Menten kinetics for this reaction, and the Km value for ATP was calculated to be 0.15 μM by the double reciprocal plot of the reaction. To elucidate the inhibition mechanism of Y-27632, the reaction was further performed in the presence of 0.3 and 1 μM Y-27632. It was shown, that the addition of Y-27632 increased the apparent Km values for ATP of ROCK-I in a concentration-dependent manner without any change in the Vmax value. These findings suggest that Y-27632 inhibited ROCK-I by competing with ATP for its binding to the kinase. Similar results were obtained with ROCK-II, and the Ki values of Y-27632 were estimated to be 0.22 and 0.30 μM for ROCK-I and ROCK-II, respectively. Selectivity of inhibition by Y-compound was then examined by comparing their Ki values for two other Rho effector kinases, citron kinase and PKN, as well as PKCα. The Ki values of the Y-compound for citron kinase and PKN were at least 20 times higher, and the Ki values for PKCα were about 200 times higher than those for ROCK kinases.
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 22:02:11 GMT 2025
by
admin
on
Mon Mar 31 22:02:11 GMT 2025
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Record UNII |
0X370ROP6H
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Record Status |
Validated (UNII)
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Record Version |
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0X370ROP6H
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300000057012
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DTXSID7043740
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DB08756
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Y-27632
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146986-50-7
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT |
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TARGET -> INHIBITOR |
Competitive with ATP
COMPETITIVE INHIBITOR
Ki
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TARGET -> INHIBITOR |