Synonym
VX702, VX 702, VX-702
IUPAC/Chemical Name
6-[(Aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-3-pyridinecarboxamide
InChi Key
FYSRKRZDBHOFAY-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
O=C(C1=CC=C(N(C(N)=O)C2=C(F)C=CC=C2F)N=C1C3=CC=C(F)C=C3F)N
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
p38 MAPK increases thromboxane levels by activating phospholipase A2, thus catalyzing the formation of arachidonic acid. VX-702 inhibited activation of p38 MAPK by thrombin, SFLLRN, AYPGKF and U46619 in platelets. Kuliopulos, A., et al. "Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation." Thromb. Haemost. 92: 1387-1393 (2004). VX-702 showed modest clinical efficacy and transient suppression of biomarkers of inflammation in patients with rheumatoid arthritis. Damjanov, N., et al. "Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies." Arthritis Rheum. 60: 1232-1241 (2009).
Preparing Stock Solutions
The following data is based on the
product
molecular weight
404.32
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
1: Wagner SJ, Skripchenko A, Seetharaman S, Kurtz J. Amelioration of lesions associated with 24-hour suboptimal platelet storage at 16 °C by a p38MAPK inhibitor, VX-702. Vox Sang. 2015 Apr;108(3):226-32. doi: 10.1111/vox.12221. Epub 2014 Dec 4. PubMed PMID: 25471280.
2: Skripchenko A, Awatefe H, Thompson-Montgomery D, Myrup A, Turgeon A, Wagner SJ. An inhibition of p38 mitogen activated protein kinase delays the platelet storage lesion. PLoS One. 2013 Aug 13;8(8):e70732. doi: 10.1371/journal.pone.0070732. eCollection 2013. PubMed PMID: 23967093; PubMed Central PMCID: PMC3742641.
3: Tamhane M, Chakilam AR, Jayaraj A, Thakkar V, Taft DR. Comparative renal excretion of VX-702, a novel p38 MAPK inhibitor, and methotrexate in the perfused rat kidney model. Drug Dev Ind Pharm. 2010 Mar;36(3):315-22. doi: 10.3109/03639040903154200. PubMed PMID: 20170280.
4: Cohen S, Fleischmann R. Kinase inhibitors: a new approach to rheumatoid arthritis treatment. Curr Opin Rheumatol. 2010 May;22(3):330-5. doi: 10.1097/BOR.0b013e3283378e6f. Review. PubMed PMID: 20164774.
5: Goldstein DM, Kuglstatter A, Lou Y, Soth MJ. Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders. J Med Chem. 2010 Mar 25;53(6):2345-53. doi: 10.1021/jm9012906. PubMed PMID: 19950901.
6: Sweeney SE. The as-yet unfulfilled promise of p38 MAPK inhibitors. Nat Rev Rheumatol. 2009 Sep;5(9):475-7. doi: 10.1038/nrrheum.2009.171. PubMed PMID: 19710669.
7: Damjanov N, Kauffman RS, Spencer-Green GT. Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41. doi: 10.1002/art.24485. Erratum in: Arthritis Rheum. 2009 Oct;60(10):3071. PubMed PMID: 19404957.
8: Genovese MC. Inhibition of p38: has the fat lady sung? Arthritis Rheum. 2009 Feb;60(2):317-20. doi: 10.1002/art.24264. PubMed PMID: 19180514.
9: Ding C. Drug evaluation: VX-702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronary syndrome. Curr Opin Investig Drugs. 2006 Nov;7(11):1020-5. PubMed PMID: 17117592.
10: Lee MR, Dominguez C. MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alpha protein. Curr Med Chem. 2005;12(25):2979-94. Review. PubMed PMID: 16378500.
11: Dominguez C, Powers DA, Tamayo N. p38 MAP kinase inhibitors: many are made, but few are chosen. Curr Opin Drug Discov Devel. 2005 Jul;8(4):421-30. Review. PubMed PMID: 16022178.
12: Kuliopulos A, Mohanlal R, Covic L. Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation. Thromb Haemost. 2004 Dec;92(6):1387-93. PubMed PMID: 15583748.
