| Chemical Properties | Back Directory | [density ]
1.32±0.1 g/cm3(Predicted) | [storage temp. ]
4°C, away from moisture and light | [form ]
Solid | [pka]
12.39±0.70(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Description]
GCS Inhibitor T-690 is a novel brain-penetrant GCS inhibitor with a lower toxicological risk, which reduced glucosylceramide in a dose-dependent manner in the plasma and cortex of mice. | [Uses]
Glucosylceramide synthase-IN-2 (compound T-690) is a potent, brain-penetrant and orally active glucosylceramide synthase (GCS) inhibitor with IC50s of 15 nM and 190 nM for human GCS and mouse GCS, respectively.Glucosylceramide synthase-IN-2 exhibits noncompetitive type inhibition with C8-ceramide and UDP-glucose.Glucosylceramide synthase-IN-2 can be used for Gaucher's disease research[1]. | [in vivo]
Glucosylceramide synthase-IN-2 (compound T-690; po; 30, 100, 300 mg/kg)?reduces GlcCer concentrations in the plasma and cerebral cortex in a dose-dependent manner in C57BL/6J mice[1].
Glucosylceramide synthase-IN-2 (po; 5 mg/kg) has a Cmax of 416 ng/mL. Glucosylceramide synthase-IN-2 shows good oral exposure (BA = 31%)[1].
Glucosylceramide synthase-IN-2 reveals good brain exposure (Cu,brain = 0.21 μM at 30 mg/kg dosing, 1 h)[1].
| [References]
[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 DOI:10.1021/acs.jmedchem.1c02078 |
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