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Blockade of GlcCer accumulation with the GlcCer synthase inhibitor Genz-123346 effectively inhibits cystogenesis in mouse models orthologous to human autosomal dominant PKD (Pkd1 conditional knockout mice) and nephronophthisis (jck and pcy mice).Molecular analysis in vitro and in vivo indicates that Genz-123346 acts through inhibition of the two key pathways dysregulated in PKD: Akt protein kinase-mammalian target of rapamycin signaling and cell cycle machinery.In the Zucker diabetic fatty rat,Genz-123346 lowered glucose and A1C levels and improved glucose tolerance. Drug treatment also prevented the loss of pancreatic beta-cell function normally observed in the Zucker diabetic fatty rat 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.
| Molecular Weight | 418.57 |
| Formula | C24H38N2O4 |
| CAS Number | 491833-30-8 |
| Solubility (25°C) | DMSO 10 mM |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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