title: A small molecule inhibitor of Bcl-2, HA14-1, also inhibits ceramide glucosyltransferase.
abstract: 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 4.5μM, 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.
authors.affiliation: Laboratory for Animal Cell Engineering, Niigata University of Pharmacy and Applied Life Sciences (NUPALS), 265-1 Higashijima, Akiha-ku, Niigata-shi, Niigata 956-8603, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Niino
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Michiyo
authors.initials: M
authors.lastname: Nagano-Ito
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ichikawa
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009570:Nitriles / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors
chemical_list: D001578:Benzopyrans; D002518:Ceramides; D004791:Enzyme Inhibitors; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; C037974:N-(7-(4-nitrobenzo-2-oxa-1,3-diazole))-6-aminocaproyl sphingosine; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase; D009327:4-Chloro-7-nitrobenzofurazan