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Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.

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.

SUBMITTER: Minus MB

PROVIDER: S-EPMC5041597 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.

Minus Matthew B MB Liu Wei W Vohidov Farrukh F Kasembeli Moses M MM Long Xin X Krueger Michael J MJ Stevens Alexandra A Kolosov Mikhail I MI Tweardy David J DJ Sison Edward Allan R EA Redell Michele S MS Ball Zachary T ZT

Angewandte Chemie (International ed. in English) 20150907 44

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, ...[more]

PMID: 26480340

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