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. SB 203580 is a p38 MAPK inhibitor. SB 203580 inhibited the ATPase activity of non-phosphorylated p38 MAPK with a Km of 9.6 mM. SB 203580 was competitive with ATP with a Ki of 21 nM, detected in a kinetic study of yeast expressed active p38 MAPK[3]. 24h treatment of SB 203580 dose-dependently inhibited IL-1β-induced PGE2 release with an EC50 of 0.18 μM[4]. SB 203580 was dissolved in drinking water at the concentration of 250 μM and orally administrated 0.4 ml/day to MRL/lpr mice aged from 14 to 22 weeks. SB203580 improved renal function by decreasing the levels of proteinuria and serum BUN, ameliorating the pathologic changes of kidney and reducing Ig and C3 depositions in the kidney. Moreover, hepatocytes necrosis, recruitment and proliferation of leucocytes in liver and spleen were found to be inhibited by administration of SB203580[5].
Adezmapimod 细胞实验
Cell Line
Concentration
Treated Time
Description
References
iPSC-HPCs
15 μM
21 days
Enhance T-cell differentiation and cell yield by strongly activating T-cell commitment genes
Nat Commun. 2021 Jan 18;12(1):430.
TNNT2 mutant iPSC-CMs
2.5 μM
72 h
SB 203580, in combination with Gö 6976, significantly improved the contractility of TNNT2 mutant iPSC-CMs and rescued mitochondrial respiration defects and ATP levels through the activation of the ATF4-dependent serine biosynthesis pathway.
Eur Heart J. 2022 Sep 21;43(36):3477-3489.
BV2 cells
10 µM
24 h
SB203580 significantly reduced the levels of NLRP3 and IL-1β and enhanced TFEB-mediated autophagy.
J Neuroinflammation. 2021 Dec 20;18(1):295.
Adezmapimod 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Acsm3 knockout mice
Intraperitoneal injection
5 mg/kg/day
Once daily for 16 days
To investigate the effect of Acsm3 knockout on metabolic syndrome and the role of the lauric acid-HNF4α-p38 MAPK axis, results showed that Acsm3 knockout led to lauric acid accumulation, activating the p38 MAPK signaling pathway and causing mitochondrial dysfunction and metabolic abnormalities.
EMBO J. 2024 Feb;43(4):507-532
Mice
Hippocampal CA1 pyramidal neurons
Intraperitoneal injection
20 mg/kg
Single injection, lasting 20 minutes
SB203580 blocked PTZ-induced Kv4.2-DPP6 complex dissociation, indicating the critical role of p38 in the dissociation of the Kv4.2-DPP6 complex.
Nat Commun. 2020 Mar 26;11(1):1567
Mice
Parkinson's disease model
Intraperitoneal injection
5 mg/kg
Every other day starting from 5 months of age until the end of 9 months
SB203580 significantly improved motor activity, reduced dopaminergic neuronal loss, and restored synaptic vesicle loss.
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