Reference - Detail
| RRC ID | 65534 |
|---|---|
| Author | Tsurumaki H, Katano H, Sato K, Imai R, Niino S, Hirabayashi Y, Ichikawa S. |
| Title | WP1066, a small molecule inhibitor of the JAK/STAT3 pathway, inhibits ceramide glucosyltransferase activity. |
| Journal | Biochem Biophys Res Commun |
| Abstract |
WP1066 is a well-known inhibitor of the JAK/STAT3 signaling pathway. By a screen of known small molecule inhibitors of various enzymes and protein factors, we identified WP1066 as a ceramide glucosyltransferase inhibitor. Ceramide glucosyltransferase catalyzes the first glycosylation step during glycosphingolipid synthesis. We found that WP1066 inhibited the activity of ceramide glucosyltransferase with an IC50 of 7.2 μM, and that its action was independent of JAK/STAT3 pathway blockade. Moreover, the modes of inhibition of ceramide glucosyltransferase were uncompetitive with respect to both C6-NBD-cermide and UDP-glucose. |
| Volume | 491(2) |
| Pages | 265-270 |
| Published | 2017-9-16 |
| DOI | 10.1016/j.bbrc.2017.07.115 |
| PII | S0006-291X(17)31473-0 |
| PMID | 28739255 |
| MeSH | 4-Chloro-7-nitrobenzofurazan / analogs & derivatives 4-Chloro-7-nitrobenzofurazan / chemistry 4-Chloro-7-nitrobenzofurazan / metabolism Animals Cell Line Ceramides / chemistry Ceramides / metabolism Enzyme Assays Enzyme Inhibitors / chemistry Enzyme Inhibitors / pharmacology* Gene Expression Glucosyltransferases / antagonists & inhibitors* Glucosyltransferases / genetics Glucosyltransferases / metabolism Humans Janus Kinases / antagonists & inhibitors Janus Kinases / genetics Janus Kinases / metabolism Kinetics Melanocytes / cytology Melanocytes / drug effects* Melanocytes / enzymology Pyridines / chemistry Pyridines / pharmacology* Rats STAT3 Transcription Factor / antagonists & inhibitors STAT3 Transcription Factor / genetics STAT3 Transcription Factor / metabolism Signal Transduction Small Molecule Libraries / chemistry Small Molecule Libraries / pharmacology* Tyrphostins / chemistry Tyrphostins / pharmacology* Uridine Diphosphate Glucose / chemistry Uridine Diphosphate Glucose / metabolism |
| IF | 2.985 |
| Resource | |
| Human and Animal Cells | B16 SK-MEL-28(RCB1930) |