TAK-715

TAK-715 is an orally active and potent p38 MAPK inhibitor with IC₅₀s of 7.1 nM, 200 nM for p38α and p38β, respectively. TAK-715 inhibits casein kinase I (CK1δ/ε) to regulate activation of Wnt/β-catenin signaling. TAK-715 shows good significant efficacy in a rat arthritis model^[1][2]. In Vitro: TAK-715 (compound 8h) inhibits LPS-stimulated release of TNF-α from THP-1 (IC₅₀=48 nM) and has no inhibitory activity for major CYPs, including CYP3A4. TAK-715 has no inhibition to p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 or TAK1 (IC₅₀>10 μM of all)^[1].
TAK 715 (10 μM; 1 hour) inhibits Wnt-3a-induced hDvl2 phosphorylation and the hDvl2 shift in U2OS-EFC cells^[2].
TAK-715 (1 μM; pretreatment for 16 hours) dramatically suppresses Norepinephrine (NE)-stimulated induction of fibronectin, CTGF, and Snai1 expression in TGF-β1-treated HK-2 cells at both the mRNA and protein levels^[3].
In Vivo: TAK-715 (compound 8h; 3-30 mg/kg; PO) significantly reduces the secondary paw volume^[1].
TAK-715 (10 mg/kg; PO) has a C_max of 0.19 μg/mL and an AUC of 1.16 μg•h/mL.