TAK-715  303162-79-0

TAK715
分子式：C24H21N3OS   分子量：399.51
 
產品描述
TAK 715是p38 MAPK抑制劑，作用于p38α，IC50為7.1 nM,作用于p38α比作用于p38β選擇性高28倍多,對p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 和 TAK1沒有抑制作用。
靶點
p38α
         
IC50
7.1 nM
         
體外研究
TAK 715 inhibits LPS-stimulated release of TNF-alpha from THP-1 with IC50 of 48 nM.TAK 715 (10 μM) inhibits Wnt-3a-induced hDvl2 phosphorylation and the hDvl2 shift in U2OS-EFC cells.The amide NH of TAK 715 is hydrogen bonded to the main-chain carbonyl of Met109 of p38 alpha. TAK 715 binds relatively high in the ATP pocket, occupying the hydrophobic back pocket, the adenine region and the front pocket of p38 as well as extending to most of the length of the Gly-rich loop.
體內研究
TAK 715 (10 mg/kg, po) inhibits LPS-induced TNF-alpha production in mice with 87.6% inhibition. TAK 715 has a modest mouse bioavailability of 18.4% and a slightly improved rat bioavailability of 21.1%. TAK 715 has a modest mouse bioavailability of 18.4% and a slightly improved rat bioavailability of 21.1%. TAK 715 results in Cmax of 0.19 μg/mL and AUC(0-24 hours) of 1.16 μg·h/mL in rats. TAK 715 (30 mg/kg, po) significantly reduces the secondary paw volume with 25 % inhibition in a rat adjuvant-induced arthritis (AA) model.
溶解性
DMSO 80 mg/mL，水 <1 mg/mL，乙醇 16 mg/mL
穩定性
2年 -20°C粉狀，6月-80°C溶于DMSO