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- Title
Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.
- Authors
Minus, Matthew B.; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M.; Long, Xin; Krueger, Michael J.; Stevens, Alexandra; Kolosov, Mikhail I.; Tweardy, David J.; Sison, Edward Allan R.; Redell, Michele S.; Ball, Zachary T.
- Abstract
Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML.
- Subjects
RHODIUM; STAT proteins; ACUTE myeloid leukemia in children; LIGAND binding (Biochemistry); SULFONAMIDES
- Publication
Angewandte Chemie, 2015, Vol 127, Issue 44, p13277
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201506889