A small molecule inhibitor of Bcl-2, HA14-1, also inhibits ceramide glucosyltransferase

HA14-1 is a Bcl-2 inhibitor that is widely used for studies of apoptosis. In the course of searching for a ceramide glucosyltransferase inhibitor that catalyzes the first glycosylation step of glycosphingolipid synthesis, we unexpectedly found that HA-14-1 also has the ability to inhibit ceramide glucosyltransferase. The IC50 value of HA14-1 against ceramide glucosyltransferase is 4.5 μM, which is lower than that reported for Bcl-2 in vitro. Kinetic analyses revealed that HA14-1 is a competitive and mixed-type inhibitor with respect to C6-NBD-ceramide and UDP-glucose, respectively.

► A Bcl-2 inhibitor, HA14-1, is a novel inhibitor of ceramide glucosyltransferase.
► HA14-1 increases intracellular ceramide level in B16 melanoma cells.
► HA14-1 could induce cell death via ceramide accumulation as well as Bcl-2 inhibition.