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Ossirene (AS101)

Cat. No. M6189
Ossirene (AS101) Structure
Synonym:

AS101

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10mg USD 120  USD120 In stock
50mg USD 450  USD450 In stock
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Quality Control & Documentation
Biological Activity

In vitro: Treatment of caspase-1 (interleukin-1 [IL-1] converting enzyme [ICE]) with Ossirene (AS101) inhibits its enzymatic activity in a dose-dependent manner. Moreover, AS101 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 AS101 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. AS101 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 AS101 (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.

In vivo: Ossirene (AS101) 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, AS101 also exerted beneficial effects. AS101 treated rats showed a large increase in SIRT1 protein levels in the liver and kidney extracts of rats treated with AS101. AS101 prevents development of insulin resistance in vivo. AS101 affects SIRT1 related metabolic pathways by changing the insulin levels. AS101 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.

Product Citations
Protocol (for reference only)
Cell Experiment
Cell lines Human peripheral blood mononuclear cells (PBMC)
Preparation method 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.
Concentrations 0.01, 0.05, 0.5, 1, 1.5, 2 μg/mL
Incubation time 24 h
Animal Experiment
Animal models c57BL/6J and BALB/c mice
Formulation PBS
Dosages 10 μg/mouse
Administration i.p.
Chemical Information
Molecular Weight 312.05
Formula C2H4Cl3O2Te.H4N
CAS Number 106566-58-9
Solubility (25°C) DMSO 12 mg/mL
Storage -20°C, dry, sealed
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 Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Shemesh II, et al. PLoS One. AS101 prevents diabetic nephropathy progression and mesangial cell dysfunction: regulation of the AKT downstream pathway.

[2] Xie L, et al. J Neuroimmunol. The immunomodulator AS101 suppresses production of inflammatory cytokines and ameliorates the pathogenesis of experimental autoimmune encephalomyelitis.

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