928320-12-1 Usage
Uses
Used in Pharmaceutical Industry:
AS 1892802 is used as a ROCK inhibitor for its potential therapeutic applications in treating inflammatory and noninflammatory arthritic pain. Its ability to inhibit PKAC-α and PRKX, along with its analgesic effects, makes it a promising candidate for the development of new treatments for pain management.
Used in Pain Management:
AS 1892802 is used as an analgesic agent for its ability to alleviate pain in rat models of inflammatory (AIA) and noninflammatory (MIA) arthritic pain. Its multi-targeted inhibition of ROCK, PKAC-α, and PRKX may contribute to its pain-relieving properties, offering a potential new approach to managing arthritic pain and other pain-related conditions.
Biological Activity
as 1892802 is a potent and selective inhibitor of rock with ic50 values of 52, 57 and 122 nm for human rock2, rat rock2 and human rock1, respectively [1].rho kinase (rock) is a serine-threonine kinase and is a downstream effector of rho, a small gtp-bound protein. rock phosphorylates target proteins such as myosin light chain kinase and lim kinase and regulates cellular shape modification, migration, growth and contraction [2].as 1892802 is a potent rock inhibitor. as 1892802 inhibited rock1 and rock2 with ic50 values of 1.69 and 0.10 μm, respectively [3]. in atdc5 cells, as1892802 induce chondrocyte differentiation. in hig82 cells, as1892802 significantly inhibited prostaglandin e2 production induced by il-1β or bradykinin [4].in both an adjuvant-induced arthritis (aia) rat model and a monoiodoacetate (mia) -induced arthritis (mia) rat model, as1892802 showed potent antinociceptive effect with ed50 value of 0.15 mg/kg [1]. in monoiodoacetate-induced arthritis and streptozotocin-induced neuropathy models, as1892802 showed analgesic effect [2]. in mia-injected rats, the mrna levels of rock i and ii increased in knee joints. as1892802 significantly inhibited cartilage damage in a dose-dependent way [4].
references
[1]. yoshimi e, kumakura f, hatori c, et al. antinociceptive effects of as1892802, a novel rho kinase inhibitor, in rat models of inflammatory and noninflammatory arthritis. j pharmacol exp ther, 2010, 334(3): 955-963.[2]. yoshimi e, yamamoto h, furuichi y, et al. sustained analgesic effect of the rho kinase inhibitor as1892802 in rat models of chronic pain. j pharmacol sci, 2010, 114(1): 119-122. [3]. li r, martin mp, liu y, et al. fragment-based and structure-guided discovery and optimization of rho kinase inhibitors. j med chem, 2012, 55(5): 2474-2478. [4]. takeshita n, yoshimi e, hatori c, et al. alleviating effects of as1892802, a rho kinase inhibitor, on osteoarthritic disorders in rodents. j pharmacol sci, 2011, 115(4): 481-489.
Check Digit Verification of cas no
The CAS Registry Mumber 928320-12-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,2,8,3,2 and 0 respectively; the second part has 2 digits, 1 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 928320-12:
(8*9)+(7*2)+(6*8)+(5*3)+(4*2)+(3*0)+(2*1)+(1*2)=161
161 % 10 = 1
So 928320-12-1 is a valid CAS Registry Number.
928320-12-1Relevant articles and documents
INHIBITORS OF RHO ASSOCIATED PROTEIN KINASES (ROCK) AND METHODS OF USE
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Page/Page column 45; 46, (2013/08/15)
Compounds and compositions having activity as inhibitors of Rho-associated proteinkinases (ROCKs), and methods of making and using the subject compounds are disclosed.
Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors
Li, Rongshi,Martin, Mathew P.,Liu, Yan,Wang, Binglin,Patel, Ronil A.,Zhu, Jin-Yi,Sun, Nan,Pireddu, Roberta,Lawrence, Nicholas J.,Li, Jiannong,Haura, Eric B.,Sung, Shen-Shu,Guida, Wayne C.,Schonbrunn, Ernst,Sebti, Said M.
, p. 2474 - 2478 (2012/05/20)
Using high concentration biochemical assays and fragment-based screening assisted by structure-guided design, we discovered a novel class of Rho-kinase inhibitors. Compound 18 was equipotent for ROCK1 (IC50 = 650 nM) and ROCK2 (IC50 = 670 nM), whereas compound 24 was more selective for ROCK2 (IC50 = 100 nM) over ROCK1 (IC50 = 1690 nM). The crystal structure of the compound 18-ROCK1 complex revealed that 18 is a type 1 inhibitor that binds the hinge region in the ATP binding site. Compounds 18 and 24 inhibited potently the phosphorylation of the ROCK substrate MLC2 in intact human breast cancer cells.
NOVEL COMPOUNDS
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Page/Page column 64, (2008/06/13)
This invention relates to novel amide derivatives and salts thereof. More particularly, it relates to novel amide derivatives and salts thereof which act as a ROCK inhibitor, to a pharmaceutical composition comprising the same and to a method of using the same therapeutically in the treatment and/or prevention of ROCK-related disease.
