Adezmapimod (SB203580)

Biological Activity

Adezmapimod (SB203580）is a P38 MAPK inhibitor with an IC50 of 0.3-0.5 μM, which is 10 times less selective than SAPK3(106T) and SAPK4(106T), and inhibits PKB phosphorylation with an IC50 of 3-5 μM.

Product Citations

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  Ecotoxicol Environ Saf. 2021 Sep 1;220:112341.

  Cadmium induces apoptosis of human granulosa cell line KGN via mitochondrial dysfunction-mediated pathways
  Adezmapimod (SB203580) purchased from AbMole

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  Ecotoxicol Environ Saf. 2021 Jan 15;208:111429.

  Bisphenol A induces apoptosis through GPER-dependent activation of the ROS/Ca 2+-ASK1-JNK pathway in human granulosa cell line KGN
  Adezmapimod (SB203580) purchased from AbMole

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  Environ Pollut. 2021 Feb 1;270:116051.

  Bisphenol AF induces apoptosis via estrogen receptor beta (ERβ) and ROS-ASK1-JNK MAPK pathway in human granulosa cell line KGN
  Adezmapimod (SB203580) purchased from AbMole

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  Cancer Immunol Res. 2020 Oct;8(10):1273-1286.

  An IL6-Adenosine Positive Feedback Loop between CD73 + γδTregs and CAFs Promotes Tumor Progression in Human Breast Cancer
  Adezmapimod (SB203580) purchased from AbMole

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  Mar Drυgs. 2020 Aug 17;18(8):429.

  Comparison of Physicochemical Characteristics and Macrophage Immunostimulatory Activities of Polysaccharides from Chlamys farreri
  Adezmapimod (SB203580) purchased from AbMole

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  Int J Oncol. 2020 Jul;57(1):197-212.

  G6PD Facilitates Clear Cell Renal Cell Carcinoma Invasion by Enhancing MMP2 Expression Through ROS‑MAPK Axis Pathway
  Adezmapimod (SB203580) purchased from AbMole

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  Toxicol Appl Pharmacol. 2020 May 15;395:114981.

  Exposure to Diisononyl Phthalate Promotes Atopic March by Activating of NF-κB and p38 MAPK
  Adezmapimod (SB203580) purchased from AbMole

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  Front Immunol. 2019 Apr 26;10:913.

  IL-12 Expands and Differentiates Human Vγ2Vδ2 T Effector Cells Producing Antimicrobial Cytokines and Inhibiting Intracellular Mycobacterial Growth.
  Adezmapimod (SB203580) purchased from AbMole

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  Food Chem Toxicol. 2018 Feb 12;114:78-87.

  Exposure to diisodecyl phthalate exacerbated Th2 and Th17-mediated asthma through aggravating oxidative stress and the activation of p38 MAPK
  Adezmapimod (SB203580) purchased from AbMole

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  Nat Commun. 2015 Jan 19;6:6018.

  Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα.
  Adezmapimod (SB203580) purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Food Chem Toxicol (2018). Figure 6. SB203580 (Abmole Bioscience, Houston, TX, USA)
	Method	i.p.
	Cell Lines	SPF (specific pathogen free) male BALB/c mice
	Concentrations	5 mg/kg
	Incubation Time	0 to 20 days
	Results	To clarify the underlying mechanism of DIDP exposure on Th17 type asthmatic lesions, SB203580 was used to block the p38 MAPK signaling pathway.

	Source	Nat Commun (2015). Figure 7. SB203580 (AbMole Bioscience)
	Method	atrial arrhythmia induction and picrosirius red-stained atrial sections
	Cell Lines
	Concentrations	i.p.4 mg/kg
	Incubation Time	6 weeks
	Results	Treatment of mice with the p38 inhibitor SB203580 during the 6-week exercise period completely prevented AF as well as atrial fibrosis.

Protocol (for reference only)

Cell Experiment
Cell lines	CT6 cells,BA/F3 cells and PBMC/T cells
Preparation method	2–5 × 106 rested CT6 cells were resuspended in 2 ml of RPMI, 5% fetal calf serum and preincubated with inhibitors or vehicle control as indicated in figure legends. Cells were then stimulated with 20 ng/ml recombinant human IL-2 for 5 min at 37 °C and pelleted in a minifuge for 30 s, medium was aspirated, and the pellet was lysed in the appropriate buffer. BA/F3 cells stably expressing deletion mutants of IL-2 receptor β chain (a generous gift from Professor T. Taniguchi, Tokyo, Japan) were maintained in glutamine containing RPMI further supplemented with 5% fetal calf serum and 0.2 μg/ml G418 (Calbiochem-Novabiochem) as described previously. Human peripheral blood mononuclear cells were prepared from buffy coat leukophoresis residues (North London Blood Transfusion Service, Colindale, London UK) and activated with 50 ng/ml OKT3 for 48 h. The cells were then washed extensively, rested overnight, and washed again before activating with IL-2; such cell preparations were >90% T cells . Cellular proliferation assays were performed by measurement of [3H]thymidine incorporation as described previously.
Concentrations	0~30 µm
Incubation time	24 h

Animal Experiment
Animal models	Systemic lupus erythematosus (SLE) model (female MRL/lpr mice and female C57BL/6 mice)
Formulation	Dissolved in drinking water (250 μM)
Dosages	0.1 M/day
Administration	orally

Chemical Information

Molecular Weight	377.43
Formula	C21H16FN3OS
CAS Number	152121-47-6
Solubility (25°C)	DMSO 43 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Zhang H, et al. Apoptosis. Induction of autophagy in hepatocellular carcinoma cells by SB203580 requires activation of AMPK and DAPK but not p38 MAPK.

[2] Barancík M, et al. Eur J Pharm Sci. SB203580, a specific inhibitor of p38-MAPK pathway, is a new reversal agent of P-glycoprotein-mediated multidrug resistance.

[3] Newton R, et al. Br J Pharmacol. The MAP kinase inhibitors, PD098059, UO126 and SB203580, inhibit IL-1beta-dependent PGE(2) release via mechanistically distinct processes.