491833-30-8
491833-30-8 structure
- Name: Genz-123346
- Chemical Name: Genz-123346
- CAS Number: 491833-30-8
- Molecular Formula: C24H38N2O4
- Molecular Weight: 418.569
- Catalog: Research Areas Metabolic Disease
- Create Date: 2017-04-01 17:32:13
- Modify Date: 2024-02-04 09:07:55
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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.
| Name | Genz-123346 |
|---|---|
| Synonyms |
N-[(1R,2R)-1-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1-hydroxy-3-(1-pyrrolidinyl)-2-propanyl]nonanamide
Nonanamide, N-[(1R,2R)-2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-hydroxy-1-(1-pyrrolidinylmethyl)ethyl]- N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)nonanamide Genz-123346 (free base) |
| Description | 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. |
|---|---|
| Related Catalog | |
| Target |
IC50: 14 nM (GM1)[1] |
| In Vitro | 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 Vivo | 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]. |
| Animal Admin | Rats: Genz-123346 is dissolved in water. Zucker diabetic fatty rats treated with Genz-123346 (75 mg/kg) for 6 weeks are fasted overnight. The following morning, the fasted rats are anesthetized and injected with 5 units human insulin into the hepatic portal vein. Quadriceps muscle and liver are harvested 2 min after injection and immediately frozen in liquid nitrogen. Insulin receptor is immunoprecipitated. The immunoprecipitates are analyzed by immunoblotting[1]. Mice: C57BL/6 mice are fed on a high-fat (45% of kcal) diet for 8 weeks, obese mice with comparable body weight gain, glucose, and insulin levels are assigned to either the treated or control groups. The mice are then gavaged daily with Genz-123346 or water for 10 weeks[1]. |
| References |
| Density | 1.1±0.1 g/cm3 |
|---|---|
| Boiling Point | 623.9±55.0 °C at 760 mmHg |
| Molecular Formula | C24H38N2O4 |
| Molecular Weight | 418.569 |
| Flash Point | 331.1±31.5 °C |
| Exact Mass | 418.283173 |
| PSA | 71.03000 |
| LogP | 4.14 |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.539 |
| Storage condition | 2-8℃ |