Y-27632

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H21N3O
Molecular Weight	247.336
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(CC[C@@H](CC1)C(=O)NC2=CC=NC=C2)[C@@H](C)N

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 8228	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 8228	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 8228	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 8228	0.3 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Systemic lupus erythematosus 16 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
Protein kinases--the major drug targets of the twenty-first century?	2002 Apr	12120282
Role of rho-kinase activity in angiotensin II-induced contraction of rabbit clitoral cavernosum smooth muscle.	2002 Dec	12494280
A role for the Rho-p160 Rho coiled-coil kinase axis in the chemokine stromal cell-derived factor-1alpha-induced lymphocyte actomyosin and microtubular organization and chemotaxis.	2002 Jan 1	11751986
Nitric oxide inhibits RhoA/Rho-kinase signaling to cause penile erection.	2002 Mar 29	11937108
Long-term effects of benidipine on cerebral vasoreactivity in hypertensive rats.	2002 Mar 8	11909606
Inhibition of Rho-kinase reduces renal Na-H exchanger activity and causes natriuresis in rat.	2003 Feb	12538827
Cardiovascular effects of Y-27632, a selective Rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model.	2003 Jan 26	12535859
Role of the small GTPase Rho in modulation of the inwardly rectifying potassium channel Kir2.1.	2003 Oct	14500755
Therapeutic significance of Y-27632, a Rho-kinase inhibitor, on the established liver fibrosis.	2003 Sep	13678700
Rho-kinase expression and its contribution to the control of perfusion pressure in the isolated rat mesenteric vascular bed.	2004 Feb 6	14757149
Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation.	2005 Aug 1	16005304
Rho-kinase (ROCK-1 and ROCK-2) upregulation in oleic acid-induced lung injury and its restoration by Y-27632.	2005 Mar 7	15740734
Synergistic effects of CoCl(2) and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells.	2006 Jul 1	16772336
Rho-kinase inhibitor, Y-27632, has an antinociceptive effect in mice.	2006 Jul 10	16750189
Defective RhoA/Rho-kinase signaling contributes to vascular hypocontractility and vasodilation in cirrhotic rats.	2006 Mar	16530523
Collagen gel contractility is enhanced in human endometriotic stromal cells: a possible mechanism underlying the pathogenesis of endometriosis-associated fibrosis.	2007 Apr	17204524
Simvastatin enhances induction of inducible nitric oxide synthase in 3T3-L1 adipocytes.	2007 Sep	17729120
Inorganic arsenic activates reduced NADPH oxidase in human primary macrophages through a Rho kinase/p38 kinase pathway.	2008 May 1	18424721
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
Phosphatase of regenerating liver-1 promotes cell migration and invasion and regulates filamentous actin dynamics.	2010 Aug	20484558
Oxidative stress and alterations in actin cytoskeleton trigger glutathione efflux in Saccharomyces cerevisiae.	2010 Dec	20708643
The protective effect of Rho-associated kinase inhibitor on aluminum-induced neurotoxicity in rat cortical neurons.	2010 Jul	20395307
Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells.	2010 Nov	20878077
Luteinizing hormone receptor-stimulated progesterone production by preovulatory granulosa cells requires protein kinase A-dependent activation/dephosphorylation of the actin dynamizing protein cofilin.	2010 Sep	20610540
Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure.	2011 Jan 1	20869980
Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway.	2011 May	21289285
Capsaicinoids regulate airway anion transporters through Rho kinase- and cyclic AMP-dependent mechanisms.	2011 Oct	21474433
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 `Thu Jul 06 13:48:31 UTC 2023` Edited by `admin` on `Thu Jul 06 13:48:31 UTC 2023`
Record UNII	0X370ROP6H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Y-27632

Common Name

English

(+)-(R)-TRANS-4-(1-AMINOETHYL)-N-(4-PYRIDYL)CYCLOHEXANECARBOXAMIDE

Systematic Name

English

J888.082D

Code

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