Genz-123346 free base

Research use only, not for human use.

Genz 123346 is an inhibitor of GL1 synthase that blocks the conversion of ceramide to GL1.

Genz-123346 is a potent and selective glucosylceramide synthase inhibitor with potential anticancer activity. Exposure of cells to Genz-123346 and to other GCS inhibitors at non-toxic 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 was primarily due to the effects on P-gp function.

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. Genz-123346(Genz) is an enhancer of autophagy flux.

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. 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.

Genz123346 | Genz-123346 | Genz 123346

Neuroscience

Gamma-secretase

GL1 synthase

Metabolic Disease

——

491833-30-8

418.57

C24H38N2O4

>98% (HPLC)

DMSO : ≥ 100 mg/mL; 238.91 mM

C(=O)(CCCCCCCC)N[C@@H]([C@H](O)c1cc2c(OCCO2)cc1)CN1CCCC1

N-[(1R,2R)-1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl]nonanamide

(-20℃)

With Ice Pack

≥ 2 years