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. Author manuscript; available in PMC: 2021 Apr 6.
Published in final edited form as: J Med Chem. 2021 Jan 4;64(1):279–297. doi: 10.1021/acs.jmedchem.0c01664

Table 1.

Representative Inhibitors of Ceramide Biosynthesis

compd target, *additional known target pharmacokinetics preliminary in vivo findings
SKI II (8)39,41 DES1 (Ki = 0.3 μM in HGC-27 cell lysates), *SK1/SK2 Orally available in mice Showed a significant inhibition of tumor growth in mice bearing JC tumors following oral admin.
P053 (29)60 CerS1 (IC50 = 0.54 μM against human CerS1) Orally available in mice Increased fatty acid oxidation in skeletal muscle and reduced overall adiposity in mice fed a high-fat diet following oral admin.
5989 aSMase (IC50 = 0.32 μM in Huh7 cell lysates) Distributed to the brain in rats (ip admin) Improved depression-like behaviors of rats, reduced the cortical and hippocampal aSMase activity, and restored neurogenesis in the brain following ip admin.
DPTIP (95)135 nSMase2 (IC50 = 0.03 μM against human nSMase2) Distributed to the brain in rats (ip admin) Attenuated IL-1β-induced ADEV release in in GFAP-GFP mice following ip admin.
PDDC (101)137,138 nSMase2 (IC50 = 0.3 μM against human nSMase2) Distributed to the brain in rats (oral admin) Attenuated IL-1β-induced ADEV release in GFAP-GFP mice following oral admin and reversed cognitive impairment in 5XFAD mice following ip admin.
106139 nSMase2 (IC50 = 0.5 μM against human nSMase2), *AChE Distributed to the brain (sc admin) Diminished IL1β-induced brain EV release in tau P301S (line PS19) mice following sc admin.