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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 of Y-27632

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

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
Rho/ROCK pathway contributes to the activation of extracellular signal-regulated kinase/GATA-4 during myocardial cell hypertrophy.
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
Rho kinase inhibitors block activation of pancreatic stellate cells.
2003 Dec
Cardiovascular effects of Y-27632, a selective Rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model.
2003 Jan 26
Effects of the Rho-kinase inhibitors, Y-27632 and fasudil, on the corpus cavernosum from diabetic mice.
2003 Jul 11
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
Functional diversity between Rho-kinase- and MLCK-mediated cytoskeletal actions in a myofibroblast-like hepatic stellate cell line.
2003 May 30
Myosin-mediated cytoskeleton contraction and Rho GTPases regulate laminin-5 matrix assembly.
2004 Feb
Differential regulation of human lung epithelial and endothelial barrier function by thrombin.
2004 Nov
Simvastatin attenuates expression of cytokine-inducible nitric-oxide synthase in embryonic cardiac myoblasts.
2005 Apr 8
Inhibition of Rho-kinase stimulates nitric oxide-independent vasorelaxation.
2005 Jan 10
Effects of ML-7 and Y-27632 on carbachol- and endothelin-1-induced contraction of bovine trabecular meshwork.
2005 Jun
Rho-kinase (ROCK-1 and ROCK-2) upregulation in oleic acid-induced lung injury and its restoration by Y-27632.
2005 Mar 7
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. II. Denervated rat bladder.
2006 Feb
An MLCK-dependent window in late G1 controls S phase entry of proliferating rodent hepatocytes via ERK-p70S6K pathway.
2006 Jul
Synergistic effects of CoCl(2) and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells.
2006 Jul 1
Role of Rho-kinase in guinea-pig gallbladder smooth muscle contraction.
2006 Mar 18
Intracellular signal transduction for migration and actin remodeling in vascular smooth muscle cells after sphingosylphosphorylcholine stimulation.
2006 Sep
Inhalation of the Rho-kinase inhibitor Y-27632 reverses allergen-induced airway hyperresponsiveness after the early and late asthmatic reaction.
2006 Sep 26
Simvastatin inhibits TNFalpha-induced invasion of human cardiac myofibroblasts via both MMP-9-dependent and -independent mechanisms.
2007 Aug
Dermal condensation formation in the chick embryo: requirement for integrin engagement and subsequent stabilization by a possible notch/integrin interaction.
2007 Mar
Simvastatin enhances induction of inducible nitric oxide synthase in 3T3-L1 adipocytes.
2007 Sep
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
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
Protective effects of Y-27632 on acute dichlorvos poisoning in rats.
2010 Mar
Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells.
2010 Nov
Regulation of retinoschisin secretion in Weri-Rb1 cells by the F-actin and microtubule cytoskeleton.
2011
Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure.
2011 Jan 1
Reactive oxygen species-dependent RhoA activation mediates collagen synthesis in hyperoxic lung fibrosis.
2011 Jun 1
Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway.
2011 May
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
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 Sat Dec 17 23:02:32 UTC 2022
Edited
by admin
on Sat Dec 17 23:02:32 UTC 2022
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
Created by admin on Sat Dec 17 23:02:32 UTC 2022 , Edited by admin on Sat Dec 17 23:02:32 UTC 2022
PRIMARY
EPA CompTox
DTXSID7043740
Created by admin on Sat Dec 17 23:02:32 UTC 2022 , Edited by admin on Sat Dec 17 23:02:32 UTC 2022
PRIMARY
DRUG BANK
DB08756
Created by admin on Sat Dec 17 23:02:32 UTC 2022 , Edited by admin on Sat Dec 17 23:02:32 UTC 2022
PRIMARY
WIKIPEDIA
Y-27632
Created by admin on Sat Dec 17 23:02:32 UTC 2022 , Edited by admin on Sat Dec 17 23:02:32 UTC 2022
PRIMARY
CAS
146986-50-7
Created by admin on Sat Dec 17 23:02:32 UTC 2022 , Edited by admin on Sat Dec 17 23:02:32 UTC 2022
PRIMARY
Related Record Type Details
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TARGET -> INHIBITOR
TARGET -> INHIBITOR