Genz-123346 free base · Synonyms: GENZ 123346 · GENZ123346

Genz-123346 free base is an orally available inhibitor of glucosylceramide synthase.

For research use only. Not for human or veterinary use.

Target Glucosylceramide Synthase (GCS)

Research area Metabolic Disease Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

Genz-123346 structure

CAS No.: 491833-30-8

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
500 mg	USD 550.00	BP-02508-500mg	In stock	Get quote
1 g	USD 785.00	BP-02508-1g	In stock	Get quote
2 g	USD 1,385.00	BP-02508-2g	In stock	Get quote
5 g	USD 2,385.00	BP-02508-5g	In stock	Get quote
10 g	Inquire	BP-02508-10g	In stock	Inquire

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Description

Genz-123346 free base is an orally available inhibitor of glucosylceramide synthase. Genz-123346 blocks the conversion of ceramide to glucosylceramide (GL1) and inhibits GM1 with an IC50 of 14 nM .

Biological activity

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. Genz-123346 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, Genz-123346 normalized A1C levels and improved glucose tolerance.

Identifiers

SMILES: CCCCCCCCC(=O)N[C@H](CN1CCCC1)[C@H](O)C1=CC=C2OCCOC2=C1
InChIKey: JMNXWOFCUJJYEO-HYBUGGRVSA-N

Specifications

MW (average): 418.5695
Formula: C₂₄H₃₈N₂O₄
CAS No.: 491833-30-8
Physical state: Solid
Color: White to off-white
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20°C 3 years; 4°C 2 years. In solvent -20°C 1 year

Solubility

Soluble in DMSO

Documents

References

[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]. Chai L, et al. The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function. Int J Oncol. 2011 Mar;38(3):701-11.

[3]. Shen W, et al. Inhibition of glucosylceramide synthase stimulates autophagy flux in neurons. J Neurochem. 2014 Jun;129(5):884-94

[4]. 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.

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