CD BioGlyco is experienced in GSL research. GSLs are commonly found in the cell membrane of eukaryotic cells. They are involved in many physiological processes on the cell surface, such as cell division, transmembrane signaling, cellular recognition, and toxin adhesion. Abnormalities in GSL metabolism are found to predispose to a variety of diseases, including GSL deposition disorders, etc. The development of GSL inhibitors will be crucial in the study of therapeutic approaches for related diseases. Currently, the development of GSL inhibitors is centered around glucosylceramide synthase (GCS). We provide various types of GSL inhibitor development services.
Fig.1 Quality GSL inhibitor development services. (CD BioGlyco)
Imino sugar is in the spotlight of drug development because it is a GCS inhibitor. Imino sugar is found to reduce GSL levels in mice. We synthesize and compare the inhibitory effects of imino sugars with different structures on GCS to identify suitable inhibitors.
1-Phenyl-2-decanoylamino-3-morpholino-propanol (PDMP) and related analogs
PDMP is the first GCS inhibitor to be characterized as reversible. The key motifs required for its activity are identified. We make modifications on this basis with the aim of synthesizing compounds with enhanced selectivity and inhibitory effects.
Other kinds of novel inhibitors
Two compounds that can inhibit GCS based on high-throughput screening are reported. We modify the structures of the published compounds based on which we try to synthesize inhibitors with stronger selectivity.
Our main strategy is to screen and synthesize compounds with strong structural homology to ceramides. We have the capability of high-throughput screening. To improve the efficiency of inhibitor development, we construct a novel compound library. It contains a wide range of natural products, synthetic compounds, etc.
Technology: High throughput screening (HTS)
Journal: ACS Medicinal Chemistry Letters
Results: In the present study, two compounds with inhibitory effects on GCS were screened and synthesized by HTS: compounds 12 and 16. These compounds were found to have better physicochemical properties and selectivity by assay. They could reduce the GlcCer content by inhibiting GCS. This study also provides a strategy for the development of GSL inhibitors: multiple fits of direct biological screening, parallel medicinal chemistry, etc.
Fig.2 GCSi effects of compound 16 on glucosylceramide production, lysosomal activity, and α-synuclein pathology in human induced pluripotent stem cells (iPSC)-derived neurons. (Roecker, et al., 2023)
At CD BioGlyco, our goal is to provide quality Glycosylation Inhibitor development services to our clients. In addition to GSL inhibitors, we also provide development services for Glycosaminoglycan Inhibitor, GPI Anchor Inhibitor, and so on. Please feel free to contact us for more detailed information about compound libraries, the GSL inhibitor development process, and so on. We look forward to providing satisfactory GSL inhibitor development services for your research projects.