| Bioactivity | 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]. | ||||||||||||
| Invitro | 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 Cmax of 0.19 μg/mL and an AUC of 1.16 μg•h/mL. Animal Model: | ||||||||||||
| Name | TAK-715 | ||||||||||||
| CAS | 303162-79-0 | ||||||||||||
| Formula | C24H21N3OS | ||||||||||||
| Molar Mass | 399.51 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [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), 5966-5979. [2]. Verkaar F, et al. Inhibition of Wnt/β-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Iδ/ɛ. Chem Biol, 2011, 18(4), 485-494. [3]. Huiwen Ren, et al. Inhibition of α1-adrenoceptor reduces TGF-β1-induced epithelial-to-mesenchymal transition and attenuates UUO-induced renal fibrosis in mice. FASEB J. 2020 Nov;34(11):14892-14904. |