Genz-123346 (free base) is an inhibitor of GL1 synthase that blocks the conversion of ceramide to GL1; inhibits GM1 with IC50 value of 14 nM. IC50: 14 nM (GM1)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.InformationGenz-123346 is an inhibitor ofGL1 synthasethat blocks the conversion of ceramide to GL1, the first step in the biosynthesis of gangliosides and other glycosphingolipids. Specification: 0.95 Molecular Formula: C24H38N2O4 Molecular Weight: 418.57 PubChem CID: 23652732 Isomeric SMILES: CCCCCCCCC(=O)N[C@H](CN1CCCC1)[C@@H](C2=CC3=C(C=C2)OCCO3)O
- UPC:
- 12352200
- Condition:
- New
- Availability:
- 2 weeks
- Weight:
- 0.96 Ounces
- HazmatClass:
- No
- WeightUOM:
- LB
- MPN:
- G413484-100mg
- CAS:
- 491833-30-8
- Product Size:
- 100mg
