SP600125

Biological Activity

SP600125 is a selective, ATP-competitive JNK inhibitor. SP600125 reversibly inhibits JNK1, 2 and 3 (IC50 = 40 - 90 nM) with negligible activity at ERK2, p38β and a range of enzymes (IC50 > 10 μM). SP600125 potently decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion via suppression of the extrinsic pathway. In cells, SP600125 dose dependently inhibited the phosphorylation of c-Jun, the expression of inflammatory genes COX-2, IL-2, IFN-gamma, TNF-alpha, and prevented the activation and differentiation of primary human CD4 cell cultures. In mice, SP600125 (15 mg/kg or 30 mg/kg) blocked lipopolysaccharide (LPS)-induced TNF-α expression and anti-CD3-induced apoptosis of CD4(+) CD8(+) thymocytes.

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
  SP600125 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
  SP600125 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
  SP600125 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
  SP600125 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
  SP600125 purchased from AbMole

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  Oncology. 2020 Jul 20.

  5-Fluorouracil enhances the chemosensitivity of gastric cancer to TRAIL via inhibition of the MAPK pathway
  SP600125 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
  SP600125 purchased from AbMole

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  Drug Des Devel Ther. 2019 Aug 12;13:2787-2798.

  Thapsigargin induces apoptosis in adrenocortical carcinoma by activating endoplasmic reticulum stress and the JNK signaling pathway: an in vitro and in vivo study.
  SP600125 purchased from AbMole

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  Cell Mol Neurobiol. 2019 Mar;39(2):301-319.

  Myosin IIA Regulated Tight Junction in Oxygen Glucose-Deprived Brain Endothelial Cells Via Activation of TLR4/PI3K/Akt/JNK1/2/14-3-3ε/NF-κB/MMP9 Signal Transduction Pathway.
  SP600125 purchased from AbMole

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  Mol Cells. 2017 May 31;40(5):363-370.

  L1 Cell Adhesion Molecule Promotes Migration and Invasion via JNK Activation in Extrahepatic Cholangiocarcinoma Cells with Activating KRAS Mutation
  SP600125 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Molecules and Cells (2017). Figure 5. SP600125 (Abmole Bioscience, USA)
	Method	Wound healing assay
	Cell Lines	EGI-1 cells
	Concentrations	10 µM
	Incubation Time
	Results	The JNK inhibitor significantly decreased cell migration and invasion, as well as JNK phosphorylation (Figs. 5A-5C), but not cell proliferation (Fig. 5D).

Protocol (for reference only)

Cell Experiment
Cell lines	A549 cells
Preparation method	Cell viability assay. Cell viability was evaluated using the Cell Counting kit (CCK)-8 assay (AbMole). In brief, the cells were seeded into 96-well plates at a density of 3×103 cells/well and left to adhere overnight. The cells were then incubated with or without 0–40 nM SP600125. Then, 100 μl CCK-8 was added and incubated in the dark at 37°C for 3 h. The absorbance was determined using the MRX II microplate reader (Dynex, Chantilly, VA, USA) at a wavelength of 450 nm.
Concentrations	0~40 nM
Incubation time	24 h

Animal Experiment
Animal models	Female CD-1 mice
Formulation	30% PEG-400/20% polypropylene glycol/15% Cremophor EL/5% ethanol/30% saline
Dosages	0, 12, 24, and 36 h, 15 mg/kg
Administration	s.c.

Chemical Information

Molecular Weight	220.23
Formula	C14H8N2O
CAS Number	129-56-6
Solubility (25°C)	DMSO 16 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] Zheng Y, et al. Exp Ther Med. JNK inhibitor SP600125 protects against lipopolysaccharide-induced acute lung injury via upregulation of claudin-4.

[2] Wang Y, et al. Life Sci. SP600125, a selective JNK inhibitor, protects ischemic renal injury via suppressing the extrinsic pathways of apoptosis.

[3] Bennett BL, et al. Proc Natl Acad Sci U S A. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase.