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Genz-123346
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Genz-123346图片
CAS NO:943344-58-9
规格:98%
分子量:987.23
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议

产品介绍
Genz-123346 is an inhibitor of GL1 synthase that blocks the conversion of ceramide to GL1; inhibits GM1 with IC50 value of 14 nM.
CAS:943344-58-9
分子式:C52H82N4O14
分子量:987.23
纯度:98%
存储:Store at -20°C

Background:

Genz-123346 is an inhibitor of GL1 synthase that blocks the conversion of ceramide to GL1; inhibits GM1 with IC50 value of 14 nM.


Exposure of cells to Genz-123346 and to other GCS inhibitors at nontoxic concentrations can enhance the killing of tumor cells by cytotoxic anti-cancer agents. Genz-123346 and a few other GCS inhibitors are substrates for multi-drug resistance efflux pumps such as P-gp (ABCB1, gP-170). In cell lines selected to over-express P-gp or which endogenously express P-gp, chemosensitization by Genz-123346 is primarily due to the effects on P-gp function[2]. Genz-123346(Genz) is an enhancer of autophagy flux[3].


In the Zucker diabetic fatty rat, Genz-123346 loared glucose and A1C levels and improved glucose tolerance. Drug treatment also prevented the loss of pancreatic beta-cell function and preserved the ability of the animals to secrete insulin. In the diet-induced obese mouse, treatment with Genz-123346 normalized A1C levels and improved glucose tolerance. The oral bioavailability of the drug is shown to be about 10% and 30% in mice and rats, respectively, with a half-life in plasma of 30-60 min[1]. Genz-123346 treatment results in a dose-dependent reduction of renal GlcCer and GM3 levels that translates into effective inhibition of cystic disease. A direct effect of Genz-123346 on the Akt-mTOR signaling pathway is observed, with reduced phosphorylation of Akt and ribosomal protein S6[4].


参考文献:
[1]. Zhao H, et al. Inhibiting glycosphingolipid synthesis improves glycemic control and insulin sensitivity in animal models of type 2 diabetes. Diabetes. 2007 May;56(5):1210-8.
[2]. Chai L, et al. The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function. Int J Oncol. 2011 Mar;38(3):701-11.
[3]. Shen W, et al. Inhibition of glucosylceramide synthase stimulates autophagy flux in neurons. J Neurochem. 2014 Jun;129(5):884-94
[4]. Natoli TA, et al. Inhibition of glucosylceramide accumulation results in effective blockade of polycystic kidney disease in mouse models. Nat Med. 2010 Jul;16(7):788-92.