AS101 is a potent Caspase-1 inhibitor which can inhibit IL-10 synthesis and potentiates IL-1α, IL-2 and TNF-α release through Caspase, performing as an immunomodulator.
AS101 is an immunomodulator which can inhibit IL-10 synthesis. The IL-10 production could be inhibited by AS101 at concentration ranging in 0.1-2.5μg/ml in a dose-dependent manner in all cell lines including B16 melanoma, stomach adenocarcinoma and GBM cells, and thus reducing clonogenicity of tumor cells. Treatment with AS101 at 1 μg/ml inhibited constitutive stat3 phosphorylation, the best characterized component of IL-10 signaling pathway, in B16 melanoma cells. Through this inhibition of constitutive Stat3 activation by virtue of the autocrine/paracrine IL-10 loop through AS101 in B16 cells, AS101 could sensitize B16 melanoma cells to chemotherapy including paclitaxel, doxorubicin and 5-fluorouracil by ~20%. And this effect could also be observed in GBM tumor model to paclitaxel via inhibition of IL-10 by administration of AS101 at dose of 0.5mg/kg, i.p.[1]. Treatment with AS101 at concentration ranging in 0.5-2.5μg/ml could increase SIRT1 levels in HEK293, HL‐60 and Rin-5f cells post 48h treatment. And robust increase of SIRT1 protein level could be observed in a time- and dose-dependent manner in livers of rats daily, i.p., dosed with 0.25-1mg/kg AS101 for 5-28 days, through a possible mechanism of serum IGF-1 reduction. Treatment with AS101 before manifestation of hyperglycemia could result in increased insulin sensitivity, and decreased blood glucose levels, and prevented symptoms of diabetes including defective glucose clearance, fatty liver, and abnormal distribution of insulin-producing beta cells in the pancreas. Also, treatment after disease emergence resulted in partial restoration of normal glucose homeostasis[2].
作用机制
AS101 may work as an ICE (interleukin-1βconverting enzyme, caspase-1) activity inhibitor.[3]
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