VX-702

• 产品号: S6005
• CAS号: 479543-46-9
• 分子式: C19H12F4N4O2
• 分子量: 404.3177928
• 保 存: -20°C

产品别名

• 标题: VX-702
• IUPAC标准名: 2-(2,4-difluorophenyl)-6-[1-(2,6-difluorophenyl)carbamoylamino]pyridine-3-carboxamide
• IUPAC传统名: 2-(2,4-difluorophenyl)-6-[1-(2,6-difluorophenyl)carbamoylamino]pyridine-3-carboxamide

产品登记号

• CAS号: 479543-46-9

产品性质

• 作用靶点: p38 MAPK
• 成盐信息: Free Base
• 溶解度: DMSO
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Research Area

• Description: Inflammation

Biological Activity

• Description: VX-702 is a highly selective inhibitor of p38 MAPKα with IC50 of 4-20 nM.
• Targets: p38 MAPKα
• IC50: 4 - 20 nM ^[1]
• In 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 C_max 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] VX-702 selectively inhibits activation of p38 MAPK after ischemia with no effects on ERKs and JNKs. The MI/AAR ratio is significantly reduced in the 50 mg/kg group compared with the 5 mg/kg and vehicle groups.^[4]
• Clinical Trials: VX-702 is currently in Phase II clinical trial in patients with rheumatoid arthritis.
• Features: VX-702 is a highly selective, orally active inhibitor of p38 MAPK

Protocol

• Protocol: Animal Study ^[3]
• Animal Models: Mouse with collagen-induced arthritis
• Doses: ≤10 mg/kg
• Administration: Administered via p.o.

References

• References: [1] Kuliopulos A, et al. Thromb Haemost, 2004, 92(6), 1387-1393.
• References: [2] Braddock M, IDDB Meeting Report, 2005, March 14-15.
• References: [3] Gill A, IDDB Meeing Report, 2002, March 06-08.
• References: [4] Bhattacharya K, et al. Circulation, 2003, 108(17), 882.

参考文献

• Kuliopulos A, et al. Thromb Haemost, 2004, 92(6), 1387-1393.
• Braddock M, IDDB Meeting Report, 2005, March 14-15.
• Gill A, IDDB Meeing Report, 2002, March 06-08.
• Bhattacharya K, et al. Circulation, 2003, 108(17), 882.