Glucosylceramide synthase-IN-2

• CAT Number: I044059
• CAS Number: 2597958-02-4
• Molecular Formula: C22H20F3N3O4
• Molecular Weight: 447.41
• Purity: ≥95%
• Synonyms: N-[4-(2-hydroxypropan-2-yl)phenyl]-3-oxo-2-[2-(2,2,2-trifluoroethoxy)phenyl]pyridazine-4-carboxamide
• InChI: InChI=1S/C22H20F3N3O4/c1-21(2,31)14-7-9-15(10-8-14)27-19(29)16-11-12-26-28(20(16)30)17-5-3-4-6-18(17)32-13-22(23,24)25/h3-12,31H,13H2,1-2H3,(H,27,29)
• InChIKey: CQAPXPSWLDAVEG-UHFFFAOYSA-N
• SMILES: CC(C)(C1=CC=C(C=C1)NC(=O)C2=CC=NN(C2=O)C3=CC=CC=C3OCC(F)(F)F)O

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].
Glucosylceramide synthase-IN-2 (compound T-690) has no SERT inhibitory activity (IC50>10 μM). Glucosylceramide synthase-IN-2 does not affect GCase activity (EC50>300 μM)[1].
Glucosylceramide synthase-IN-2 (30 μM) does not potently inhibit hERG, CaV1.2, and NaV1.5 channels[1].
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].

Reference

[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
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