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 8297	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 8297	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 8297	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 8297	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
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
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
Effects of cell tension on the small GTPase Rac.	2002 Jul 8	12105187
Nitric oxide inhibits RhoA/Rho-kinase signaling to cause penile erection.	2002 Mar 29	11937108
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
Rho kinase inhibitors block activation of pancreatic stellate cells.	2003 Dec	14581180
Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta.	2003 Feb	12605241
Rho kinase mediates serum-induced contraction in fibroblast fibers independent of myosin LC20 phosphorylation.	2003 Mar	12388108
Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho.	2003 Nov 14	14615541
Therapeutic significance of Y-27632, a Rho-kinase inhibitor, on the established liver fibrosis.	2003 Sep	13678700
Vanadate activates Rho A translocation in association with contracting effects in ileal longitudinal smooth muscle of guinea pig.	2004 Aug	15286430
Role of Rho-kinase in maintaining airway smooth muscle contractile phenotype.	2004 Jan 1	14709328
Differential effects of simvastatin on mesangial cells.	2004 Jul	15200425
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
Rho kinase expression and its central role in ovine gallbladder contractions elicited by a variety of excitatory stimuli.	2005 Dec 28	16324691
Simvastatin inhibits MMP-9 secretion from human saphenous vein smooth muscle cells by inhibiting the RhoA/ROCK pathway and reducing MMP-9 mRNA levels.	2005 May	15728660
Trapidil inhibits platelet-derived growth factor-induced migration via protein kinase A and RhoA/Rho-associated kinase in rat vascular smooth muscle cells.	2005 May 16	15894306
Thrombin-induced contraction in alveolar epithelial cells probed by traction microscopy.	2006 Aug	16675616
Azithromycin has a direct relaxant effect on precontracted airway smooth muscle.	2006 Dec 28	17070799
M2 and M3 muscarinic receptor activation of urinary bladder contractile signal transduction. II. Denervated rat bladder.	2006 Feb	16243962
Rho-kinase inhibitor, Y-27632, has an antinociceptive effect in mice.	2006 Jul 10	16750189
Role of Rho-kinase in guinea-pig gallbladder smooth muscle contraction.	2006 Mar 18	16499905
Collagen gel contractility is enhanced in human endometriotic stromal cells: a possible mechanism underlying the pathogenesis of endometriosis-associated fibrosis.	2007 Apr	17204524
Simvastatin inhibits TNFalpha-induced invasion of human cardiac myofibroblasts via both MMP-9-dependent and -independent mechanisms.	2007 Aug	17560598
Nitric oxide does not downregulate Rho-kinase (ROCK-2) expression in rat coronary endothelial cells.	2008 Feb	18287881
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
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
Protective effects of Y-27632 on acute dichlorvos poisoning in rats.	2010 Mar	20223382
Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral neuropathy induced by anti-cancer drug cisplatin.	2010 Mar	20060419
Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure.	2011 Jan 1	20869980
Capsaicinoids regulate airway anion transporters through Rho kinase- and cyclic AMP-dependent mechanisms.	2011 Oct	21474433
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.	2011 Oct 30	22037377
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
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 `Sat Dec 16 08:22:38 GMT 2023` Edited by `admin` on `Sat Dec 16 08:22:38 GMT 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