AS601245 is an inhibitor of the c-Jun NH2-terminal kinase (JNK) (hJNK1: IC50=150nM, hJNK2: IC50=220nM and hJNK3: IC50=70 nM), has neuroprotective properties.

98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

JNK Inhibitor V

DMSO ≥35 mg/mL

JNK

AS601245 inhibits isolated hJNK3 in an ATP-competitive manner. Selectivity of AS601245 is tested against a large panel of kinases. AS601245 exhibits 10- to 20-fold selectivity over c-src, CDK2, and c-Raf and more than 50- to 100-fold selectivity over a range of Ser/Thr- and Tyr-protein kinases. The effects of AS601245 and Clofibrate alone or in association are analysed on proliferation, apoptosis, differentiation and the gene expression profile of CaCo-2 human colon cancer cells. Reduction of cell proliferation, accompanied by the modulation of p21 expression is observed in HepG2 cells, also. 5 μM Clofibrate, 0.1 μM AS601245, and the combined treatment with the two substances do not cause acute toxicity in HepG2 cells. All treatments reduce cell proliferation starting from 48 hours after the beginning of experiments, and the inhibitory effect reaches the maximum at 72 hours.

AS601245 is a potent inhibitor of LPS-induced TNF-α release in mice. Administered orally at 0.3, 1, 3, and 10 mg/kg, AS601245 decreases the TNF-α release in a dose-dependent manner. AS601245 (40, 60, and 80 mg/kg) administered i.p. provides significant protection against the delayed loss of hippocampal CA1 neurons in a gerbil model of transient global ischemia. This effect is mediated by JNK inhibition and therefore by c-Jun expression and phosphorylation. A significant neuroprotective effect of AS601245 administered either by i.p. injection (6, 18, and 60 mg/kg) or as i.v. bolus (1 mg/kg) followed by an i.v. infusion (0.6 mg/kg/h) is also observed in rats after focal cerebral ischemia.

1. Carboni S, et al. Br J Pharmacol. 2008 Jan;153(1):157-163.