UGT8-IN-1

• CAT Number: I037809
• CAS Number: 2414349-93-0
• Molecular Formula: C20H22F6N4O4S
• Molecular Weight: 528.47
• Purity: ≥95%
• Synonyms: [1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] N-[(2S)-1-(trifluoromethoxy)propan-2-yl]carbamate
• InChI: InChI=1S/C20H22F6N4O4S/c1-10(8-33-20(24,25)26)28-18(32)34-11-3-5-30(6-4-11)14-7-13(19(21,22)23)16-15(29-14)12(9-35-16)17(31)27-2/h7,9-11H,3-6,8H2,1-2H3,(H,27,31)(H,28,32)/t10-/m0/s1
• InChIKey: UQQUABVWYAPTIQ-JTQLQIEISA-N
• SMILES: CC(COC(F)(F)F)NC(=O)OC1CCN(CC1)C2=NC3=C(C(=C2)C(F)(F)F)SC=C3C(=O)NC

UGT8-IN-1 is a brain penetrable and orally active inhibitor of ceramide galactosyltransferase enzyme (UGT8). UGT8-IN-1 can be used in the study for lysosomal storage disorders[1].
UGT8-IN-1 (compound 19) exhibits the T1/2 of 4.3 h, 1.13 h and 13.6 h by iv (1 mg/kg) administration in rat, mouse and dog, respectively. UGT8-IN-1 (compound 19) shows F% of 40%, 34% and 52% by oral (3 mg/kg) administration in rat, mouse and dog, respectively[1].
UGT8-IN-1 (compound 19, orally twice a day for three days) shows ≥90% inhibition of incorporation of 13C-Gal into GalCer and SFT, at all three doses tested, with the estimated ED50s of <3 mg/kg for inhibition of both SFT and GalCer. UGT8-IN-1 (compound 19) has very high plasma protein and tissue binding (>99%)[1].

Reference

[1]. Sukanthini Thurairatnam, et al. Brain Penetrable Inhibitors of Ceramide Galactosyltransferase for the Treatment of Lysosomal Storage Disorders. ACS Med Chem Lett. 2020 Jun 16;11(10):2010-2016.
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