VX-702 is a highly specific p38α MAPK inhibitor, 14-fold higher selectivity for the p38α than p38β. VX-702 is a small molecule investigational oral anti-cytokine therapy for treatment of inflammatory diseases, specifically rheumatoid arthritis (RA).

p38α:4 nM-20 nM

每天两次VX-702（0.1 mg/kg）处理与甲胺喋呤（0.1 mg/kg）处理效果接近.此外,每天两次VX-702（5 mg/kg）处理与每天一次氢化泼尼松（10 mg/kg）处理效果类似.与对照组和用5 mg/kg VX-702处理实验组相比,50 mg/kg实验组的MI/AAR比率显著降低.VX-702半衰期为16-20 h,半数清除剂量3.75 L,分布容积为73 L/kg. VX-702对p38 MAPK活性具有选择性抑制作用,但不影响ERKs和JNKs.

VX-702不影响p38 MAPK兴奋剂诱导的血小板聚集。用VX-702（1 μM）处理血小板,可完全或部分抑制由血小板兴奋剂(包括凝血酵素,AYPGKF,SFLLRN,U46619和胶原)诱导的p38活性（IC50：4-20 nM）。VX-702剂量依赖性地抑制IL-6（IC50：59 ng/ml）、IL-1β（IC50：122 ng/ml）和TNFα（IC50：99 ng/ml）的产生。

HDAC enzyme assay in vitro: The deacetylase enzyme assay is based on a homogeneous fluorescence release assay. Purified recombinant HDAC enzymes are incubated with MGCD0103 diluted in various concentrations for 10 minutes in assay buffer [25 mM HEPES (pH 8.0), 137 mM NaCl, 1 mM MgCl2, 2.7 mM KCl] at room temperature. The substrate Boc-Lys(ε-Ac)-AMC is added to the reaction for further incubation at 37 °C. The concentration of the substrate and the incubation time varies for different isotypes of HDAC enzymes. A 20-min trypsin incubation at room temperature allows the release of the fluorophore from the deacetylated substrate. The fluorescent signal is detected by fluorometer at excitation of 360 nm, emission of 470 nm, and cutoff at 435 nm.