Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C14H21N3O.2ClH |
| Molecular Weight | 320.258 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 3 / 3 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.[H][C@@]1(CC[C@@H](CC1)C(=O)NC2=CC=NC=C2)[C@@H](C)N
InChI
InChIKey=IDDDVXIUIXWAGJ-LJDSMOQUSA-N
InChI=1S/C14H21N3O.2ClH/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);2*1H/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 |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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) |
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
| 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 |
|
| 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 |
|
| Effects of cell tension on the small GTPase Rac. | 2002 Jul 8 |
|
| 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 |
|
| Involvement of Rho-kinase pathway for angiotensin II-induced plasminogen activator inhibitor-1 gene expression and cardiovascular remodeling in hypertensive rats. | 2002 May |
|
| Inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathway induces apoptosis in human endothelial cells. | 2002 May 3 |
|
| Cerivastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, inhibits cardiac myocyte hypertrophy induced by endothelin. | 2002 Oct 25 |
|
| Inhibitory effect of fluvastatin on lysophosphatidylcholine-induced nonselective cation current in Guinea pig ventricular myocytes. | 2002 Sep |
|
| Rho kinase inhibitors block activation of pancreatic stellate cells. | 2003 Dec |
|
| Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta. | 2003 Feb |
|
| 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 |
|
| 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 |
|
| Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors to proliferation of astrocytes. | 2003 Nov |
|
| Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho. | 2003 Nov 14 |
|
| 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 |
|
| Vanadate activates Rho A translocation in association with contracting effects in ileal longitudinal smooth muscle of guinea pig. | 2004 Aug |
|
| Role of Rho-kinase in maintaining airway smooth muscle contractile phenotype. | 2004 Jan 1 |
|
| Differential effects of simvastatin on mesangial cells. | 2004 Jul |
|
| Differential regulation of human lung epithelial and endothelial barrier function by thrombin. | 2004 Nov |
|
| 8-Bromo-cAMP decreases the Ca2+ sensitivity of airway smooth muscle contraction through a mechanism distinct from inhibition of Rho-kinase. | 2004 Oct |
|
| Rho kinase expression and its central role in ovine gallbladder contractions elicited by a variety of excitatory stimuli. | 2005 Dec 28 |
|
| 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 |
|
| Azithromycin has a direct relaxant effect on precontracted airway smooth muscle. | 2006 Dec 28 |
|
| M2 and M3 muscarinic receptor activation of urinary bladder contractile signal transduction. I. Normal rat bladder. | 2006 Feb |
|
| Rho-kinase inhibitor, Y-27632, has an antinociceptive effect in mice. | 2006 Jul 10 |
|
| Intracellular signal transduction for migration and actin remodeling in vascular smooth muscle cells after sphingosylphosphorylcholine stimulation. | 2006 Sep |
|
| 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 |
|
| Combined inhibition of Cdk5 and ROCK additively increase cell survival, but not the regenerative response in regenerating retinal ganglion cells. | 2009 Dec |
|
| Suppression of hepatitis C virus replication by protein kinase C-related kinase 2 inhibitors that block phosphorylation of viral RNA polymerase. | 2009 Oct |
|
| Statin's excitoprotection is mediated by sAPP and the subsequent attenuation of calpain-induced truncation events, likely via rho-ROCK signaling. | 2009 Sep 9 |
|
| Up-regulation of the RhoA/Rho-kinase signaling pathway in corpus cavernosum from endothelial nitric-oxide synthase (NOS), but not neuronal NOS, null mice. | 2010 Apr |
|
| Oxidative stress and alterations in actin cytoskeleton trigger glutathione efflux in Saccharomyces cerevisiae. | 2010 Dec |
|
| 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 |
|
| Protective effects of Y-27632 on acute dichlorvos poisoning in rats. | 2010 Mar |
|
| Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral neuropathy induced by anti-cancer drug cisplatin. | 2010 Mar |
|
| Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells. | 2010 Nov |
|
| 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 |
|
| Capsaicinoids regulate airway anion transporters through Rho kinase- and cyclic AMP-dependent mechanisms. | 2011 Oct |
|
| A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. | 2013 Apr 15 |
|
| Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy. | 2013 Apr 30 |
|
| 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
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
Sat Dec 17 22:26:10 UTC 2022
by
admin
on
Sat Dec 17 22:26:10 UTC 2022
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| Record UNII |
Q9828II7F3
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| Record Status |
Validated (UNII)
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| Record Version |
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Q9828II7F3
Created by
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129830-38-2
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DTXSID3042635
Created by
admin on Sat Dec 17 22:26:10 UTC 2022 , Edited by admin on Sat Dec 17 22:26:10 UTC 2022
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PARENT -> SALT/SOLVATE |
