TAK-715 is ap38 MAPK inhibitor for p38α with IC50 of 7.1 nM, being 28-fold selective for p38α over p38β, showing no inhibition to p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 or TAK1.
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.
TAK-715 is a p38 MAPK inhibitor, with selectivity for p38α. The inhibitory IC50 of TAK-715 against p38α was 7.1nM while the data against p38β was 200nM. TAK-715 was not active against p38γ, p38δ, or other kinases. TAK-715 inhibited LPS-stimulated release of TNFα from THP-1 cells with an IC50 of 48 nM[3]. At the concentration of 10μM, TAK-715 inhibited Wnt-3a-induced hDvl2 phosphorylation and the hDvl2 shift in U2OS-EFC cells[4]. Orally administrated at the dose of 10mg/kg, TAK-715 resulted in 87.6% inhibition of LPS-induced TNFα production in mice. In an adjuvant-induced arthritis model in rats, TAK-715 dose dependently inhibited paw swelling when given daily for 14 days at 3mg/kg, 10mg/kg or 30mg/kg[3].
作用机制
TAK-715 target p38α in an ATP-competitive manner[4].
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