UGT8 inhibitor 19 is a highly potent, selective and orally active ceramide galactosyltransferase enzyme UGT8 inhibitor with IC50 of 0.2 nM.
UGT8 inhibitor 19 is selective for inhibition of UGT8 compared to other UGT enzymes (IC50 > 10 μM for UGT1A1, UGT1A6, UGT2B7, UGT2B15, and UGT2B17) and a Cerep panel of around 60 kinases.
UGT8 inhibitor 19 demonstrated dose dependent inhibition of incorporation of 13C-Gal into GalCer and SFT in adult mice kidney with an estimated ED50 of 1 mg/kg for inhibition of both SFT and GalCer.
UGT8 inhibitor 19 showed efficacy in the in vivo pharmacodynamic models, indicating the potential to treat metachromatic leukodystrophy (MLD).
