In vitro: Treatment of caspase-1 (interleukin-1 [IL-1] converting enzyme [ICE]) with 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: 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.
|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 models||c57BL/6J and BALB/c mice|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.
|Solubility||62 mg/mL in DMSO|
AS101 prevents diabetic nephropathy progression and mesangial cell dysfunction: regulation of the AKT downstream pathway.
Shemesh II, et al. PLoS One. 2014 Dec 4;9(12):e114287. PMID: 25474550.
The immunomodulator AS101 suppresses production of inflammatory cytokines and ameliorates the pathogenesis of experimental autoimmune encephalomyelitis.
Xie L, et al. J Neuroimmunol. 2014 Aug 15;273(1-2):31-41. PMID: 24975323.
Acecainide HCl, also known as N-acetylprocainamide and ASL 601, is the N-acetylated metabolite of procainamide.
Sematilide (CK-1752) hydrochloride is a novel class III antiarrhythmic agent.
EBE-A22 is a derivative of PD 153035, has no effect on EGF-R TK but maintains a high cytotoxic profile.
NIH-12848 is a putative phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ) inhibitor.
CHS-828 (GMX1778) is a potent and specific inhibitor of NAMPT with IC50 and Kd value of <25 nM and 120 nM, respectively.
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