Brief Description

Genz-123346 free base is an inhibitor of GL1 synthase that blocks the conversion of ceramide to GL1; IC50 for GM1 inhibition is 14 nM.
IC50 value: 14 nM [1]
Target: GlcCer synthase inhibitor
in vitro: Unlike N-butyldeoxynojirimycin (NB-DNJ), which is another inhibitor of GL1 synthase, Genz-123346 does not inhibit α-glucosidase or glucocerebrosidase [1].
in vivo: 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 [1]. 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) [2].
References on Genz-123346 free base
[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]. 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.

Solubility

10 mM in DMSO

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

White to off-white solid