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].
TAK-715 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human adipose stem cells (hASCs)
10 µM
12 days
TAK-715 significantly suppressed lipid accumulation during the differentiation of hASCs and downregulated the phosphorylation of p38 MAPK.
Life (Basel). 2023 Feb 1;13(2):412.
Rat NPCs
0, 0.05, 0.1, 0.25, 0.5, 1.0, 5, 10 µM
24 and 48 hours
To evaluate the cytotoxicity of TAK-715 on NPCs, the results showed that TAK-715 was not toxic to NPCs at concentrations below 1.0 μM and could slightly decrease the cellular activity of NPCs
Arthritis Res Ther. 2023 Mar 21;25(1):45.
3T3-L1 preadipocytes
10 µM
8 days
TAK-715 significantly suppressed lipid accumulation and intracellular triglyceride content during the differentiation of 3T3-L1 preadipocytes, and downregulated the expression and phosphorylation of C/EBP-α, PPAR-γ, STAT-3, FAS, perilipin A, p38 MAPK, and its downstream effector ATF-2.
Life (Basel). 2023 Feb 1;13(2):412.
TAK-715 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
SD rats
Puncture-induced intervertebral disc degeneration model
Intradiscal injection
5 μl (1 μM)
Single injection
To evaluate the ameliorative effect of TAK-715 on intervertebral disc degeneration in vivo, the results showed that TAK-715 delayed disc degeneration by inhibiting NPC apoptosis and ECM degradation
搜索
