An inhibitor of p38α MAPK
TAK-715 is a selective inhibitor of p38 MAPK with IC50 value of 7.1 nM [1].
p38 mitogen-activated protein (MAP) kinases (p38 MAPKs) are a class of mitogen-activated protein kinases and play an important role in controlling cellular responses to cytokines and stress. Four p38 MAPKs contain members, p38-α (MAPK14), p38-β (MAPK11), p38-γ (MAPK12/ERK6), and p38-δ (MAPK13/SAPK4), have been identified. Abnormal expression of p38 MAPKs are correlated with a variety of chronic inflammatory diseases and their inhibitors are regarded as promising targets in clinical [1] [2].
TAK-715 is a potent p38 MAPK inhibitor and has a different selectivity with the reported p38 MAPK inhibitor VX-745. When tested with human monocytic THP-1 cells, administration of TAK-715 exhibited inhibition on p38MAPKα with IC50 value of 7.1 nM [1]. In HEK293T, U2OS, and F9 cells, TAK-715 was used to inhibit p38 MAPK activity and concluded that p38 MAPK had no function in Wnt/β-catenin signaling pathway [2].
In adjuvant-induced rheumatoid arthritis rat model, administration of TAK-715 at dose of 10 mg/kg significantly decreased LPS-induced stimulated release of TNF-α (87.6%) by inhibiting p38 MAPK activity [1].
参考文献:
[1].? Miwatashi, S., et al., Novel inhibitor of p38 MAP kinase as an anti-TNF-alpha drug: discovery of N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (TAK-715) as a potent and orally active anti-rheumatoid arthritis agent. J Med Chem, 2005. 48(19): p. 5966-79.
[2].?? Verkaar, F., et al., Inhibition of Wnt/beta-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Idelta/varepsilon. Chem Biol, 2011. 18(4): p. 485-94.
动态评分
0.0