VX 702
Names
[ CAS No. ]:
745833-23-2
[ Name ]:
VX 702
[Synonym ]:
6-[Carbamoyl(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)nicotinamide
3-Pyridinecarboxamide, 6-[(aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-
VX702
Biological Activity
[Description]:
VX-702 is a highly selective inhibitor of p38α MAPK(IC50=4 -20 nM), 14-fold higher potency against the p38α versus p38β.IC50 value: 4-20 nM [1]Target: p38α MAPKin vitro: Pre-incubation of platelets with VX-702 (1 μM) completely or partially inhibits p38 activation (IC50 4 to 20 nM) induced by platelet agonists including thrombin, SFLLRN, AYPGKF, U46619 and collagen. VX-702 shows no effect on platelet aggregation induced by any of the p38 MAPK agonists in the presence or absence of anti-platelet therapies [1]. VX-702 inhibits the production of IL-6, IL-1β and TNFα (IC50 = 59, 122 and 99 ng/mL, respectively) in a dose-dependent manner [2]. in vivo: The half-life of VX-702 is 16 to 20 hours, with a median clearance of 3.75 L/h and a volume of distribution of 73 L/kg. Both AUC and Cmax values are dose proportional for VX-702, which is predominantly cleared renally [2]. VX-702 (at a dose of 0.1 mg/kg twice daily) has an equivalent effect as that of methotrexate (0.1 mg/kg). In addition, VX-702 (5 mg/kg twice daily) also has an equivalent effect as prednisolone (10 mg/kg once daily), as measured by percentage inhibition of wrist joint erosion and inflammation score [3].
[Related Catalog]:
[References]
[1]. Kuliopulos A, et al. Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation. Thromb Haemost, 2004, 92(6), 1387-1393.
[2]. Braddock M, IDDB Meeting Report, 2005, March 14-15.
[3]. Gill A, IDDB Meeing Report, 2002, March 06-08.
[4]. Naka K, et al. Dipeptide species regulate p38MAPK-Smad3 signalling to maintain chronic myelogenous leukaemia stem cells. Nat Commun. 2015 Aug 20;6:8039.
[Related Small Molecules]
Chemical & Physical Properties
[ Density]:
1.5±0.1 g/cm3
[ Boiling Point ]:
555.2±60.0 °C at 760 mmHg
[ Molecular Formula ]:
C19H12F4N4O2
[ Molecular Weight ]:
404.318
[ Flash Point ]:
289.6±32.9 °C
[ Exact Mass ]:
404.089630
[ PSA ]:
102.31000
[ LogP ]:
0.76
[ Vapour Pressure ]:
0.0±1.5 mmHg at 25°C
[ Index of Refraction ]:
1.629
[ Storage condition ]:
-20°C