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
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
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Q13464 Gene ID: 6093.0 Gene Symbol: ROCK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9353125 |
0.22 µM [Ki] | ||
Target ID: O75116 Gene ID: 9475.0 Gene Symbol: ROCK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382 |
0.3 µM [Ki] | ||
Target ID: Q13464 Gene ID: 6093.0 Gene Symbol: ROCK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382 |
0.22 µM [IC50] | ||
Target ID: O75116 Gene ID: 9475.0 Gene Symbol: ROCK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382 |
0.3 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Preventing | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
Protein kinases--the major drug targets of the twenty-first century? | 2002 Apr |
|
Role of rho-kinase activity in angiotensin II-induced contraction of rabbit clitoral cavernosum smooth muscle. | 2002 Dec |
|
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 |
|
Nitric oxide inhibits RhoA/Rho-kinase signaling to cause penile erection. | 2002 Mar 29 |
|
Long-term effects of benidipine on cerebral vasoreactivity in hypertensive rats. | 2002 Mar 8 |
|
Inhibition of Rho-kinase reduces renal Na-H exchanger activity and causes natriuresis in rat. | 2003 Feb |
|
Cardiovascular effects of Y-27632, a selective Rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model. | 2003 Jan 26 |
|
Role of the small GTPase Rho in modulation of the inwardly rectifying potassium channel Kir2.1. | 2003 Oct |
|
Therapeutic significance of Y-27632, a Rho-kinase inhibitor, on the established liver fibrosis. | 2003 Sep |
|
Rho-kinase expression and its contribution to the control of perfusion pressure in the isolated rat mesenteric vascular bed. | 2004 Feb 6 |
|
Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation. | 2005 Aug 1 |
|
Rho-kinase (ROCK-1 and ROCK-2) upregulation in oleic acid-induced lung injury and its restoration by Y-27632. | 2005 Mar 7 |
|
Synergistic effects of CoCl(2) and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells. | 2006 Jul 1 |
|
Rho-kinase inhibitor, Y-27632, has an antinociceptive effect in mice. | 2006 Jul 10 |
|
Defective RhoA/Rho-kinase signaling contributes to vascular hypocontractility and vasodilation in cirrhotic rats. | 2006 Mar |
|
Collagen gel contractility is enhanced in human endometriotic stromal cells: a possible mechanism underlying the pathogenesis of endometriosis-associated fibrosis. | 2007 Apr |
|
Simvastatin enhances induction of inducible nitric oxide synthase in 3T3-L1 adipocytes. | 2007 Sep |
|
Inorganic arsenic activates reduced NADPH oxidase in human primary macrophages through a Rho kinase/p38 kinase pathway. | 2008 May 1 |
|
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 |
|
Phosphatase of regenerating liver-1 promotes cell migration and invasion and regulates filamentous actin dynamics. | 2010 Aug |
|
Oxidative stress and alterations in actin cytoskeleton trigger glutathione efflux in Saccharomyces cerevisiae. | 2010 Dec |
|
The protective effect of Rho-associated kinase inhibitor on aluminum-induced neurotoxicity in rat cortical neurons. | 2010 Jul |
|
Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells. | 2010 Nov |
|
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 |
|
Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure. | 2011 Jan 1 |
|
Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway. | 2011 May |
|
Capsaicinoids regulate airway anion transporters through Rho kinase- and cyclic AMP-dependent mechanisms. | 2011 Oct |
|
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
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10779382
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
Edited
Thu Jul 06 13:48:31 UTC 2023
by
admin
on
Thu Jul 06 13:48:31 UTC 2023
|
Record UNII |
0X370ROP6H
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
0X370ROP6H
Created by
admin on Thu Jul 06 13:48:32 UTC 2023 , Edited by admin on Thu Jul 06 13:48:32 UTC 2023
|
PRIMARY | |||
|
DTXSID7043740
Created by
admin on Thu Jul 06 13:48:32 UTC 2023 , Edited by admin on Thu Jul 06 13:48:32 UTC 2023
|
PRIMARY | |||
|
DB08756
Created by
admin on Thu Jul 06 13:48:32 UTC 2023 , Edited by admin on Thu Jul 06 13:48:32 UTC 2023
|
PRIMARY | |||
|
Y-27632
Created by
admin on Thu Jul 06 13:48:32 UTC 2023 , Edited by admin on Thu Jul 06 13:48:32 UTC 2023
|
PRIMARY | |||
|
146986-50-7
Created by
admin on Thu Jul 06 13:48:32 UTC 2023 , Edited by admin on Thu Jul 06 13:48:32 UTC 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
TARGET -> INHIBITOR | |||
|
SALT/SOLVATE -> PARENT | |||
|
TARGET -> INHIBITOR |