Glucosylceramide synthase-IN-1 (T-036) a potent, brain-penetrant and orally active glucosylceramide synthase (GCS) inhibitor with IC50s of 31 nM and 51 nM for human GCS and mouse GCS, respectively. Glucosylceramide synthase-IN-1 can be used for Gaucher's disease research[1].
Glucosylceramide synthase-IN-1 (T-036) potently reduces the GCS product, catalyze glucosylceramide (GlcCer), in the fibroblasts with Gaucher's disease (EC50 of 7.6 nM)[1].
Glucosylceramide synthase-IN-1 (T-036) has good oral exposure (BA = 67%) and moderate brain penetration (Kpuu,brain = 0.11). Administration of a single dose of Glucosylceramide synthase-IN-1 (T-036) reduces GlcCer in the plasma and cerebral cortex of wild-type mice, and administration of Glucosylceramide synthase-IN-1 (T-036) for 2 months significantly reduces glucosylsphingosine (GlcSph) in the cerebral cortex of the Gaucher's disease mouse model[1].
[1]. Yuta Tanaka, et al. Discovery of Brain-Penetrant Glucosylceramide Synthase Inhibitors with a Novel Pharmacophore. J Med Chem. 2022 Mar 10;65(5):4270-4290