生物活性

• 描述The stress-activated protein kinase (SAPK) p38 isoforms are mitogen-activated protein kinase (MAPK) family members. MAPKs act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The well reported isoforms of p38 MAPKs include p38α, p38β and others. VX-702 is a selective inhibitor of p38α MAPK. VX-702 inhibited the activation of platelet MAPK-activated protein kinase-2, the substrate of p38α MAPK with IC₅₀s ranging from 4 – 20 nM^[3]. In an ex vivo blood assay primed with LPS, VX-702 dose-dependently inhibited the production of IL-6, IL-1β and TNFα with IC₅₀s of 59, 122 and 99 ng/ml, respectively ^[4]. In collagen-induced mouse arthritis model, VX-702 dosed at 0.1 mg/kg twice daily or 5 mg/kg twice daily were of equivalent therapeutic effects to methotrexate or prednisolone at the same doses, as measured by the percentage inhibition of wrist joint erosion and an inflammation score^[4]. In a rat model of ischemia-reperfusion injury, VX-702 orally administrated at the doses of 5 or 50 mg/kg dose-dependently reduced the increase of phosphor MK2 in the ischemic zone tissue, and the MI/AAR ratio was significantly reduced in the 50 mg/kg VX-702 treated group^[4].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HOP-62 cell	-	Growth inhibition assay	-	Inhibition of human HOP-62 cell growth in a cell viability assay, IC50=0.01543 μM	SANGER
  human A2780 cell	-	Growth inhibition assay	-	Inhibition of human A2780 cell growth in a cell viability assay, IC50=21.8225 μM	SANGER
  human A388 cell	-	Growth inhibition assay	-	Inhibition of human A388 cell growth in a cell viability assay, IC50=7.80384 μM	SANGER

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• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00205478	Rheumatoid Arthritis	Phase 2	Completed	-	-
  NCT00395577	Rheumatoid Arthritis	Phase 2	Completed	-	Bulgaria ... more >> Call For Information Dimitrovgrad, Bulgaria Call For Information Pleven, Bulgaria Call For Information Sofia, Bulgaria Call For Information Veliko Tarnovo, Bulgaria Croatia Call For Information Osijek, Croatia Call For Information Zagreb, Croatia Former Serbia and Montenegro Call For Information Belgrade, Former Serbia and Montenegro Call For Information Niska Banja, Former Serbia and Montenegro Call For Information Zemun, Former Serbia and Montenegro Poland Call For Information Bytom, Poland Call For Information Krakow, Poland Call for Information Torun, Poland Call For Information Zyrardow, Poland Russian Federation Call For Information Novosibirsk, Russian Federation Call For Information Saratov, Russian Federation Call For Information St. Petersburg, Russian Federation Slovenia Call For Information Ljubljana, Slovenia Collapse <<

• 参考文献

• [1] Naka K, Jomen Y, et al. Dipeptide species regulate p38MAPK-Smad3 signalling to maintain chronic myelogenous leukaemia stem cells. Nat Commun. 2015 Aug 20;6:8039.

  [2] Kuliopulos A, Mohanlal R, et al. Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation. Thromb Haemost. 2004 Dec;92(6):1387-93.

  [3] 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.

  [4] 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.