U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

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
Structure of Y-27632

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

HIDE SMILES / InChI

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q13464
Gene ID: 6093.0
Gene Symbol: ROCK1
Target Organism: Homo sapiens (Human)
0.22 µM [Ki]
Target ID: O75116
Gene ID: 9475.0
Gene Symbol: ROCK2
Target Organism: Homo sapiens (Human)
0.3 µM [Ki]
Target ID: Q13464
Gene ID: 6093.0
Gene Symbol: ROCK1
Target Organism: Homo sapiens (Human)
0.22 µM [IC50]
Target ID: O75116
Gene ID: 9475.0
Gene Symbol: ROCK2
Target Organism: Homo sapiens (Human)
0.3 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
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
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
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
Cardiovascular effects of Y-27632, a selective Rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model.
2003 Jan 26
Rho kinase mediates serum-induced contraction in fibroblast fibers independent of myosin LC20 phosphorylation.
2003 Mar
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
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

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
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 Mon Mar 31 22:02:11 GMT 2025
Edited
by admin
on Mon Mar 31 22:02:11 GMT 2025
Record UNII
0X370ROP6H
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
J888.082D
Preferred Name English
Y-27632
Common Name English
(+)-(R)-TRANS-4-(1-AMINOETHYL)-N-(4-PYRIDYL)CYCLOHEXANECARBOXAMIDE
Systematic Name English
CYCLOHEXANECARBOXAMIDE, 4-(1-AMINOETHYL)-N-4-PYRIDINYL-, (4(R)-TRANS)-
Systematic Name English
4.BETA.-((1R)-1-AMINOETHYL)-N-(4-PYRIDINYL)CYCLOHEXANE-1.ALPHA.-CARBOXAMIDE
Systematic Name English
CYCLOHEXANECARBOXAMIDE, 4-((1R)-1-AMINOETHYL)-N-4-PYRIDINYL-, TRANS-
Systematic Name English
Y 27632 [WHO-DD]
Common Name English
Code System Code Type Description
FDA UNII
0X370ROP6H
Created by admin on Mon Mar 31 22:02:12 GMT 2025 , Edited by admin on Mon Mar 31 22:02:12 GMT 2025
PRIMARY
SMS_ID
300000057012
Created by admin on Mon Mar 31 22:02:12 GMT 2025 , Edited by admin on Mon Mar 31 22:02:12 GMT 2025
PRIMARY
EPA CompTox
DTXSID7043740
Created by admin on Mon Mar 31 22:02:12 GMT 2025 , Edited by admin on Mon Mar 31 22:02:12 GMT 2025
PRIMARY
DRUG BANK
DB08756
Created by admin on Mon Mar 31 22:02:12 GMT 2025 , Edited by admin on Mon Mar 31 22:02:12 GMT 2025
PRIMARY
WIKIPEDIA
Y-27632
Created by admin on Mon Mar 31 22:02:12 GMT 2025 , Edited by admin on Mon Mar 31 22:02:12 GMT 2025
PRIMARY
CAS
146986-50-7
Created by admin on Mon Mar 31 22:02:11 GMT 2025 , Edited by admin on Mon Mar 31 22:02:11 GMT 2025
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
Competitive with ATP
COMPETITIVE INHIBITOR
Ki
TARGET -> INHIBITOR