Sinbaglustat

Sinbaglustat (OGT2378) is a dual inhibitor of glucosylceramide synthase (GCS) and non-lysosomal glucosyl ceramidase (GBA2). Sinbaglustat is an orally available N-alkyl iminosugar that crosses the blood-brain barrier. Sinbaglustat can be used for the research of central neurodegenerative diseases associated with lysosomal dysfunctions. sinbaglustat (OGT2378) is a GCS inhibitor (Glucosyl Ceramide Synthase Inhibitor) with potential anticancer activity. In murine models with melanoma, OGT2378 decreased tumor size, and showed no cytotoxic and apoptotic effects on MEB-4 melanomacells. Additionally, it has been reported that OGT2378 is biologically active, and a well tolerated agent in in vivo system.

Product information

CAS Number: 441061-33-2

Molecular Weight: 233.30

Formula: C11H23NO4

Chemical Name: (2S, 3R, 4R, 5S)-2-(hydroxymethyl)-1-pentylpiperidine-3, 4, 5-triol

Smiles: CCCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@@H]1CO

InChiKey: HCZQIIVHWYFIPW-UKKRHICBSA-N

InChi: InChI=1S/C11H23NO4/c1-2-3-4-5-12-6-9(14)11(16)10(15)8(12)7-13/h8-11,13-16H,2-7H2,1H3/t8-,9-,10+,11+/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: To be determined

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Sinbaglustat (OGT2378; 20 μM) reduces the synthesis of glucosylceramide and ganglioside by 93% and >95% in MEB4 melanoma cells compared with untreated MEB4 cells, respectively, without either cytotoxic or antiproliferative effects. GBA2 is an enzyme involved in the catabolism of glycosphingolipids (GSLs). Sinbaglustat is 50-fold more potent in inhibiting GBA2 than GCS.

In Vivo:

Sinbaglustat (OGT2378; administered p.o., in the powdered chow, at a dose of 2500 mg/kg/day, corresponding to 35-40 mg of Sinbaglustat per mouse per day) is highly effective in impeding melanoma tumor growth in vivo. The effectiveness of p.o. Sinbaglustat in this murine model suggests that inhibition of glycosphingolipid synthesis is a promising approach to inhibit tumor progression.

References:

1. Martine Gehin, et al. Assessment of Target Engagement in a First-in-Human Trial with Sinbaglustat, an Iminosugar to Treat Lysosomal Storage Disorders. Clin Transl Sci. 2021 Mar;14(2):558-567.
2. Michael Weiss, et al. Inhibition of melanoma tumor growth by a novel inhibitor of glucosylceramide synthase. Cancer Res. 2003 Jul 1;63(13):3654-8.

Products are for research use only. Not for human use.