209410-46-8 Usage
Description
VX-745 is a potent and selective inhibitor of p38α mitogen-activated protein (MAP) kinase, belonging to the class of pyrimidopyridazines. It is characterized by its pale yellow solid appearance and has a high selectivity for p38α over other kinases such as p38β MAPK, ERK, JNK, and a panel of 50 kinases when used at a concentration of 2 μM.
Uses
Used in Pharmaceutical Industry:
VX-745 is used as a potential anti-inflammatory agent for its ability to inhibit the production of IL-1β and TNF-α in isolated human peripheral blood mononuclear cells (PBMCs) with IC50s of 45 and 51 nM, respectively.
Used in Treatment of Werner Syndrome:
VX-745 is used as a potential therapeutic agent for Werner syndrome, a genetic disorder characterized by accelerated aging, due to its inhibitory effects on p38α MAPK.
Used in Treatment of Inflammatory Diseases:
VX-745 is used as a potential treatment for inflammatory diseases, such as arthritis. It has been shown to reduce disease severity in a type II collagen-induced mouse model of arthritis when administered at a dose of 10 mg/kg.
Biochem/physiol Actions
VX-745 is a selective blood-brain barrier penetrant inhibitor of p38 MAPKα. VX-745 showed 20-fold selectivity for p38α over p38β and a Ki value of 220 nM. VX-745 has been shown to reduce inflammation in an arthritic (AIA) mouse model and to improve performance in aged rats.
references
[1]. bagley, m.c., et al., microwave-assisted ullmann c-s bond formation: synthesis of the p38alpha mapk clinical candidate vx-745. j org chem, 2009. 74(21): p. 8336-42.[2]. dent, p., et al., mapk pathways in radiation responses. oncogene, 2003. 22(37): p. 5885-96.[3]. dominguez, c., d.a. powers, and n. tamayo, p38 map kinase inhibitors: many are made, but few are chosen. curr opin drug discov devel, 2005. 8(4): p. 421-30.[4]. duffy, j.p., et al., the discovery of vx-745: a novel and selective p38alpha kinase inhibitor. acs med chem lett, 2011. 2(10): p. 758-63.[5]. bagley, m.c., et al., gram-scale synthesis of the p38alpha mapk-inhibitor vx-745 for preclinical studies into werner syndrome. future med chem, 2010. 2(9): p. 1417-27.
Check Digit Verification of cas no
The CAS Registry Mumber 209410-46-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,0,9,4,1 and 0 respectively; the second part has 2 digits, 4 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 209410-46:
(8*2)+(7*0)+(6*9)+(5*4)+(4*1)+(3*0)+(2*4)+(1*6)=108
108 % 10 = 8
So 209410-46-8 is a valid CAS Registry Number.
InChI:InChI=1/C19H9Cl2F2N3OS/c20-11-2-1-3-12(21)17(11)18-14-5-7-16(25-26(14)9-24-19(18)27)28-15-6-4-10(22)8-13(15)23/h1-9H