VX-702

VX-702, one of a series of second-generation, is an orally active p38 MAP kinase inhibitors, for the potential treatment of inflammation, rheumatoid arthritis and cardiovascular diseases. VX-702 prevents activation of p38MAPK and decrements in many platelet storage parameters after exposure to 16 °C without agitation for 24 h.

Product information

CAS Number: 745833-23-2

Molecular Weight: 404.32

Formula: C19H12F4N4O2

Synonym:

VX702

VX 702

Related CAS Number:

479543-46-9 (Deleted CAS#)

Chemical Name: 6-[(Aminocarbonyl)(2, 6-difluorophenyl)amino]-2-(2, 4-difluorophenyl)-3-pyridinecarboxamide

Smiles: NC(=O)N(C1C(F)=CC=CC=1F)C1=CC=C(C(=N1)C1=CC=C(F)C=C1F)C(N)=O

InChiKey: FYSRKRZDBHOFAY-UHFFFAOYSA-N

InChi: InChI=1S/C19H12F4N4O2/c20-9-4-5-10(14(23)8-9)16-11(18(24)28)6-7-15(26-16)27(19(25)29)17-12(21)2-1-3-13(17)22/h1-8H,(H2,24,28)(H2,25,29)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Solubility (25°C) DMSO: 81 mg/mL(200.34 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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. 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.

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. 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. 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.

References:

1. Gill A, IDDB Meeing Report, 2002, March 06-08.
2. Braddock M, IDDB Meeting Report, 2005, March 14-15.
3. Kuliopulos A, et al. Thromb Haemost, 2004, 92(6), 1387-1393.

Products are for research use only. Not for human use.