Y-27632

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382 | https://www.ncbi.nlm.nih.gov/pubmed/28122300 |https://www.ncbi.nlm.nih.gov/pubmed/26673160

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	Potency
Rho-associated protein kinase 1 20 Target ID: Q13464 Gene ID: 6093.0 Gene Symbol: ROCK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9353125	Inhibitor 8504	0.22 µM [Ki]
Rho-associated protein kinase 2 25 Target ID: O75116 Gene ID: 9475.0 Gene Symbol: ROCK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382	Inhibitor 8504	0.3 µM [Ki]
Rho-associated protein kinase 1 20 Target ID: Q13464 Gene ID: 6093.0 Gene Symbol: ROCK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382	Inhibitor 8504	0.22 µM [IC50]
Rho-associated protein kinase 2 25 Target ID: O75116 Gene ID: 9475.0 Gene Symbol: ROCK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382	Inhibitor 8504	0.3 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Systemic lupus erythematosus 15 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28122300	Preventing		Basic research	Unknown Approved Use Unknown
Corneal edema 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26393474	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
		252160361
Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension.	1997 Oct 30	9353125
Y-27632 potentiates relaxant effects of beta 2-adrenoceptor agonists in bovine tracheal smooth muscle.	2000 Feb 11	10686302
Long-term effects of benidipine on cerebral vasoreactivity in hypertensive rats.	2002 Mar 8	11909606
Involvement of Rho-kinase pathway for angiotensin II-induced plasminogen activator inhibitor-1 gene expression and cardiovascular remodeling in hypertensive rats.	2002 May	11961044
Cerivastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, inhibits cardiac myocyte hypertrophy induced by endothelin.	2002 Oct 25	12398901
Inhibitory effect of fluvastatin on lysophosphatidylcholine-induced nonselective cation current in Guinea pig ventricular myocytes.	2002 Sep	12181436
Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta.	2003 Feb	12605241
Cardiovascular effects of Y-27632, a selective Rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model.	2003 Jan 26	12535859
Rho kinase mediates serum-induced contraction in fibroblast fibers independent of myosin LC20 phosphorylation.	2003 Mar	12388108
Involvement of Rho-kinase in P2Y-receptor-mediated contraction of renal glomeruli.	2003 Mar 21	12646249
Vanadate activates Rho A translocation in association with contracting effects in ileal longitudinal smooth muscle of guinea pig.	2004 Aug	15286430
Rho-kinase expression and its contribution to the control of perfusion pressure in the isolated rat mesenteric vascular bed.	2004 Feb 6	14757149
8-Bromo-cAMP decreases the Ca2+ sensitivity of airway smooth muscle contraction through a mechanism distinct from inhibition of Rho-kinase.	2004 Oct	15121638
Upregulation of Rho-kinase (ROCK-2) expression and enhanced contraction to endothelin-1 in the mesenteric artery from lipopolysaccharide-treated rats.	2004 Sep 13	15363997
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	15621049
Screening for cell migration inhibitors via automated microscopy reveals a Rho-kinase inhibitor.	2005 Mar	15797222
Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts.	2005 Oct	16030252
Thrombin-induced contraction in alveolar epithelial cells probed by traction microscopy.	2006 Aug	16675616
Roles of stretch-activated cation channel and Rho-kinase in the spontaneous contraction of airway smooth muscle.	2006 Dec 15	17026989
M2 and M3 muscarinic receptor activation of urinary bladder contractile signal transduction. I. Normal rat bladder.	2006 Feb	16243961
Role of Rho-kinase in guinea-pig gallbladder smooth muscle contraction.	2006 Mar 18	16499905
Beneficial effects of the Rho kinase inhibitor Y27632 in murine puromycin aminonucleoside nephrosis.	2008	18367845
Nitric oxide does not downregulate Rho-kinase (ROCK-2) expression in rat coronary endothelial cells.	2008 Feb	18287881
Simvastatin inhibits central sympathetic outflow in heart failure by a nitric-oxide synthase mechanism.	2008 Jul	18441251
Inorganic arsenic activates reduced NADPH oxidase in human primary macrophages through a Rho kinase/p38 kinase pathway.	2008 May 1	18424721
Dual pathway activated by tert-butyl hydroperoxide in human airway anion secretion.	2008 Nov	18664589
Effects of a selective Rho-kinase inhibitor Y-27632 on oxidative stress parameters in acute dichlorvos poisoning in rats.	2008 Oct	18636419
Calcium sensitization in human esophageal muscle: role for RhoA kinase in maintenance of lower esophageal sphincter tone.	2008 Oct	18628484
Combined inhibition of Cdk5 and ROCK additively increase cell survival, but not the regenerative response in regenerating retinal ganglion cells.	2009 Dec	19782753
Agonist-biased signaling via proteinase activated receptor-2: differential activation of calcium and mitogen-activated protein kinase pathways.	2009 Oct	19605524
Suppression of hepatitis C virus replication by protein kinase C-related kinase 2 inhibitors that block phosphorylation of viral RNA polymerase.	2009 Oct	19243496
Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor.	2009 Sep	19597037
Statin's excitoprotection is mediated by sAPP and the subsequent attenuation of calpain-induced truncation events, likely via rho-ROCK signaling.	2009 Sep 9	19741129
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	19896475
The protective effect of Rho-associated kinase inhibitor on aluminum-induced neurotoxicity in rat cortical neurons.	2010 Jul	20395307
Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account.	2010 Jun 1	20462760
Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral neuropathy induced by anti-cancer drug cisplatin.	2010 Mar	20060419
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.	2011 Oct 30	22037377
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	22226621
Critical roles of Rho-associated kinase in membrane blebbing and mitochondrial pathway of apoptosis caused by 1-butanol.	2012 Sep	22564901
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.	2013 Apr 15	23398362
Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy.	2013 Apr 30	23376009
RhoGEF17, a Rho-specific guanine nucleotide exchange factor activated by phosphorylation via cyclic GMP-dependent kinase Iα.	2013 Mar	23195829
ROCK-dependent ATP5D modulation contributes to the protection of notoginsenoside NR1 against ischemia-reperfusion-induced myocardial injury.	2014 Dec 15	25305180
The role of Rho-kinases in IL-1β release through phagocytosis of fibrous particles in human monocytes.	2015 Jan	24760326

Patents

Sample Use Guides

In Vivo Use Guide

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

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

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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