Ossirene (AS101), a potent in vitro and in vivo immunomodulator, is a novel inhibitor of IL-1beta converting enzyme.

Treatment of caspase-1 (interleukin-1 [IL-1] converting enzyme [ICE]) with Ossirene inhibits its enzymatic activity in a dose-dependent manner. Moreover, Ossirene treatment causes a significant reduction in the active form of IL-18 and IL-1 in peripheral blood mononuclear cells (PBMC) and in human HaCat keratinocytes. The inhibitory effect of Ossirene does not involve nitric oxide (NO) or interferon- (IFN- ), two possible regulators of IL-18 production, and does not occur at the mRNA level. It may exert effects through a posttranscriptional mechanism[1]. Ossirene induced SIRT1 expression in a dose dependent manner in three different cell lines, HEK293, HL-60 and Rin-5f. Incubation of HEK293 and HL-60 cell lines with Ossirene (0.1-2.5μg/ml) resulted in a dose dependent reduction in PPARγ protein expression relative to the control cells, and the reduction of PPARγ expression is in parallel to increased SIRT1 expression[2].

Ossirene downregulates IL-18 and IL-1 serum levels in a mouse model of lipopolysaccharide (LPS)-induced sepsis, resulting in increased survival. It has also been shown to be protective against lethal and sublethal effects of irradiation and chemotherapy. In a model of cecal ligation and puncture (CLP)-induced sepsis in mice, Ossirene also exerted beneficial effects[1]. Ossirene treated rats showed a large increase in SIRT1 protein levels in the liver and kidney extracts of rats treated with Ossirene. Ossirene prevents development of insulin resistance in vivo. Ossirene affects SIRT1 related metabolic pathways by changing the insulin levels. Ossirene treatment prevents hyperglycemia associated with T2D(type 2 diabetes) and some of the symptoms of the disease in the HFD(high fat diet)+STZ(Streptozotocin) rat model[2].

In vitro, PBMCs were first treated with various concentrations of AS101, and after 1 h SAC (10-3 v/v) was added. After 24 h, supernatants were collected and evaluated for cytokine content. (Only for Reference)

DMSO: 5.63 mg/mL (18.04 mM), Sonication is recommended.