DES1 Inhibitor

SKI-II is a commonly used inhibitor of both sphingosine kinase I (SPHK1) and 2 (SPHK2). Recently it has been shown to inhibit dihydroceramide desaturase (Des1) which Aurelio et al. suggest is actually responsible for its anti-proliferative activity, not SPHK inhibition. Compound 34 is an analog of SKI-II and is a selective Des1 inhibitor which shows no activity against either SPHK1 or SPHK2. 34 inhibits PC3 cell growth (GIC50 = 0.34 μM) but some of this may be due to inhibition of another target

References

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L. Aurelio, C.V. Scullino, et al.. “From Sphingosine Kinase to Dihydroceramide desaturase: A Structure?Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II)” J. Med. Chem., 59, 965-984, DOI: 10.1021/acs.jmedchem.5b01439.