Rhodium(II) proximity-labeling identifies a novel target site on STAT3 for inhibitors with potent anti-leukemia activity
Open accessAbstract
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.
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STAT3 inhibitors-SF-1-066, BP-1-102, and MM206-may, in addition to binding to the SH2 domain, affect the function of the SH2 domain by binding to and perturbing the structure of domains of STAT3 at a distance from the SH2 domain, suggesting an allosteric destabilizing effect on the SH2 domain.
“For example, hydrogen–deuterium exchange experiments and other studies show that STAT3 inhibitors—SF-1-066, BP-1-102, and MM206—may, in addition to binding to the SH2 domain, affect the function of the SH2 domain by binding to and perturbing the structure of domains of STAT3 at a distance from the SH2 domain, suggesting an allosteric destabilizing effect on the SH2 domain (Resetca et al., 2014;”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Minus et al., 2015
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References 35 · Cited by 38
Research works printed but not linked: 31
- [1]Canner J Alonzo TA Franklin J Freyer DR Gamis A Gerbing RB Lange BJ Meshinchi S Woods WG Perentesis J Horan J Cancer 2013 119 4162 24104395 PMC4398142
- [2]Redell MS Ruiz MJ Alonzo TA Gerbing RB Tweardy DJ Blood 2011 117 5701 21447830 PMC3110027
- [3]Yu CL Meyer DJ Campbell GS Larner AC Carter-Su C Schwartz J Jove R Science 1995 269 81 7541555
- [4]Bromberg JF Wrzeszczynska MH Devgan G Zhao Y Pestell RG Albanese C Darnell JE Jr Cell 1999 98 295 10458605
- [5]Liu LJ Leung KH Chan DSH Wang YT Ma DL Leung CH Cell Death Dis 2014 5 e1293 24922077 PMC4611723
- [6]Zhang X Yue P Page BDG Li T Zhao W Namanja AT Paladino D Zhao J Chen Y Gunning PT Turkson J Proc. Nat. Acad. Sci. U.S.A 2012 109 9623 PMC3386073 22623533
- [7]Shahani VM Yue P Haftchenary S Zhao W Lukkarila JL Zhang X Ball D Nona C Gunning PT Turkson J ACS Med. Chem. Lett 2011 2 79 21243039 PMC3021410
- [8]Shahani VM Yue P Fletcher S Sharmeen S Sukhai MA Luu DP Zhang X Sun H Zhao W Schimmer AD Turkson J Gunning PT Bioorg. Med. Chem 2011 19 1823 21216604 PMC3151534
- [9]Page BDG Fletcher S Yue P Li Z Zhang X Sharmeen S Datti A Wrana JL Trudel S Schimmer AD Turkson J Gunning PT Bioorg. Med. Chem. Lett 2011 21 5605 21788134 PMC4530782
- [10]Kraskouskaya D Duodu E Arpin CC Gunning PT Chem. Soc. Rev 2013 42 3337 23396540
- [11]Morlacchi P Robertson FM Klostergaard J McMurray JS Future Med. Chem 2014 6 1909 25495984 PMC4339284
- [12]Zhou L Kawate T Liu X Kim YB Zhao Y Feng G Banerji J Nash H Whitehurst C Jindal S Siddiqui A Seed B Wolfe JL Biorg. Med. Chem 2012 20 750 22217933
- [13]Xu X Kasembeli MM Jiang X Tweardy BJ Tweardy DJ PLoS ONE 2009 4 e4783 19274102 PMC2653189
- [14]Vohidov F Knudsen SE Leonard PG Ohata J Wheadon MJ Popp BV Ladbury JE Ball ZT Chem. Sci 2015 6 4778 PMC5667506 29142714
- [15]Kundu R Cushing PR Popp BV Zhao Y Madden DR Ball ZT Angew. Chem. Int. Ed 2012 51 7217 PMC3677582 22700245 Kundu R Cushing PR Popp BV Zhao Y Madden DR Ball ZT Angew. Chem 2012 124 7329 PMC3677582 22700245
- [16]Tishinov K Schmidt K Häussinger D Gillingham DG Angew. Chem. Int. Ed 2012 51 12000 23090851 Tishinov K Schmidt K Häussinger D Gillingham DG Angew. Chem 2012 124 12166 23090851
- [17]Antos JM McFarland JM Iavarone AT Francis MB J. Am. Chem. Soc 2009 131 6301 19366262 PMC2722835
- [18]Ball ZT Acc. Chem. Res 2013 46 560 23210518
- [19]Vohidov F Coughlin JM Ball ZT Angew. Chem. Int. Ed 2015 54 4587 25688989 Kundu R Cushing PR Popp BV Zhao Y Madden DR Ball ZT Angew. Chem 2012 124 7329 PMC3677582 22700245
- [21]Zhang T Kee WH Seow KT Fung W Cao X Mol. Cell. Biol 2000 20 7132 10982829 PMC86266
- [22]Neculai D Neculai AM Verrier S Straub K Klumpp K Pfitzner E Becker S J. Biol. Chem 2005 280 40782 16192273
- [23]Ren Z Mao X Mertens C Krishnaraj R Qin J Mandal PK Romanowski MJ McMurray JS Chen X Biochem. Biophys. Res. Commun 2008 374 1 18433722
- [24]Nkansah E Shah R Collie GW Parkinson GN Palmer J Rahman KM Bui TT Drake AF Husby J Neidle S Zinzalla G Thurston DE Wilderspin AF FEBS Lett 2013 587 833 23434585
- [25]Jones RB Gordus A Krall JA MacBeath G Nature 2006 439 168 16273093
- [26]Mace PD Wallez Y Dobaczewska MK Lee JJ Robinson H Pasquale EB Riedl SJ Nat. Struct. Mol. Biol 2011 18 1381 22081014 PMC3230775
- [27]Taylor JD Ababou A Fawaz RR Hobbs CJ Williams MA Ladbury JE Proteins: Struct., Funct., Bioinf 2008 73 929 18536014
- [28]Sargent JM Elgie AW Williamson CJ Hill BT Anti-Cancer Drugs 2003 14 467 12853890
- [29]Kluza J Mazinghien R Irwin H Hartley JA Bailly C Anti-Cancer Drugs 2006 17 155 16428933
- [30]Kirby S Gertler SZ Mason W Watling C Forsyth P Aniagolu J Stagg R Wright M Powers J Eisenhauer EA Neuro-Oncology 2005 7 183 15831236 PMC1871890
- [31]Rubenstein SM Baichwal V Beckmann H Clark DL Frankmoelle W Roche D Santha E Schwender S Thoolen M Ye Q Jaen JC J. Med. Chem 2001 44 3599J Med. Chem 11606124
- [32]Furuichi Y Goi K Inukai T Sato H Nemoto A Takahashi K Akahane K Hirose K Honna H Kuroda I Zhang X Kagami K Hayashi Y Harigaya K Nakazawa S Sugita K Cancer Res 2007 67 9852 17942916
- Authors
- Minus, M. B., Liu, W., Vohidov, F., Kasembeli, M. M., Long, X., Krueger, M. J., Stevens, A., Kolosov, M. I., Tweardy, D. J., Sison, E. A. R., Redell, M. S., & Ball, Z. T.
- Affiliations
- Rice University (US)
- Baylor College of Medicine (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Tweardy, David J.
- Sison, Edward Allan R.
- Redell, Michele S.
- Ball, Zachary T.
- ORCID
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2015-09-07
- Volume
- 54
- Issue
- 44
- Pages
- 13085-13089
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- PMC
- PMC5041597
- OpenAlex
- W2158236694
- Cited by
- 38
- References
- 35
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 6 · 2017: 2 · 2016: 4
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rice Research Repository (Rice University) (acceptedVersion)
- Funders
- NIH (F31CA180696, 5R21CA170625, R41CA153658)
- Robert A. Welch Foundation (C-1680)
- National Science Foundation (CHE-1055569)
- Gillson Longenbaugh Foundation
- Virginia and L.E. Simmons Family Foundation
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Keywords
- STAT3, acute myeloid leukemia, rhodium(II) catalysis, proximity labeling, coiled-coil domain, STAT3 inhibitor, chemoresistance, relapsed leukemia, ligand binding sites
- MeSH terms
- Animals, Antineoplastic Agents, Binding Sites, Catalysis, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Naphthalenes, Neoplasms, Experimental, Rhodium, Structure-Activity Relationship, Sulfonamides, Leukemia, Myeloid, Acute, Apoptosis, Cell Proliferation, STAT3 Transcription Factor, Mice
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