Acid ceramidase (aCDase) is a lysosomal amidase which hydrolyzes the acyl chain from ceramides forming sphingosine which is subsequently phosphorylated to the bioactive lipid sphingosine 1-phosphate. aCDase is upregulated in many cancer types such as melanoma, prostate, head, neck, and colon cancers. ARN14988 is a potent inhibitor of aCDase in vitro (IC50 = 12 nM) and in A375 melanoma cells (IC50 = 1.5uM). ARN14988 is weakly cytotoxic by itself, but shows a synergystic effect with some common anti-cancer drugs (5-Fluorouracil, vemurafinib, and taxol) in proliferative G361 cells.
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