Nanomolar-potency small molecule inhibitor of STAT5 protein
| Autor: | D.B. Diaz, David E. Muench, Mulu Geletu, Minden, Abbarna A. Cumaraswamy, Laister Rc, Andrew M. Lewis, C.E. Brown, A. Todic, Kagan Kerman, Patrick T. Gunning, H.L. Grimes, Xin R. Cheng |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Letter
biology Organic Chemistry leukemia cells food and beverages Pharmacology Biochemistry Small molecule In vitro Cell biology Protein–protein interaction chemistry.chemical_compound chemistry Apoptosis hemic and lymphatic diseases Drug Discovery biology.protein protein−protein interactions anticancer drug MCL1 STAT3 Lead compound STAT5 small-molecule inhibitor |
| Zdroj: | ACS Medicinal Chemistry Letters |
| Popis: | © 2014 American Chemical Society. We herein report the design and synthesis of the first nanomolar binding inhibitor of STAT5 protein. Lead compound 13a, possessing a phosphotyrosyl-mimicking salicylic acid group, potently and selectively binds to STAT5 over STAT3, inhibits STAT5-SH2 domain complexation events in vitro, silences activated STAT5 in leukemic cells, as well as STAT5's downstream transcriptional targets, including MYC and MCL1, and, as a result, leads to apoptosis. We believe 13a represents a useful probe for interrogating STAT5 function in cells as well as being a potential candidate for advanced preclinical trials. |
| Databáze: | OpenAIRE |
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