A selective small-molecule STAT5 PROTAC degrader capable of achieving tumor regression in vivo

Kaneshige, Atsunori; Bai, Longchuan; Wang, Mi; McEachern, Donna; Meagher, Jennifer L.; Xu, Renqi; Wang, Yu; Jiang, Wei; Metwally, Hoda; Kirchhoff, Paul D.; Zhao, Lijie; Jiang, Hui; Wang, Meilin; Wen, Bo; Sun, Duxin; Stuckey, Jeanne A.; Wang, Shaomeng

doi:10.1038/s41589-022-01248-4

A selective small-molecule STAT5 PROTAC degrader capable of achieving tumor regression in vivo

Journal Article · 01 February 2023 · Nature Chemical Biology

DOI:https://doi.org/10.1038/s41589-022-01248-4· OSTI ID:2423268

; Bai, Longchuan; Wang, Mi; McEachern, Donna; Meagher, Jennifer L.; Xu, Renqi; Wang, Yu; Jiang, Wei; Metwally, Hoda; Kirchhoff, Paul D.; Zhao, Lijie; ; ; ; ; ; Wang, Shaomeng

Not provided.

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC02-06CH11357

OSTI ID:: 2423268

Journal Information:: Nature Chemical Biology, Journal Name: Nature Chemical Biology Journal Issue: 6 Vol. 19; ISSN 1552-4450

Publisher:: Nature Publishing Group

Country of Publication:: United States

Language:: English

References (50)

Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
GenePattern 2.0 Reich, Michael; Liefeld, Ted; Gould, Joshua Nature Genetics, Vol. 38, Issue 5 https://doi.org/10.1038/ng0506-500	journal	May 2006
Small molecule targeting of the STAT5/6 Src homology 2 (SH2) domains to inhibit allergic airway disease Knight, J. Morgan; Mandal, Pijus; Morlacchi, Pietro Journal of Biological Chemistry, Vol. 293, Issue 26 https://doi.org/10.1074/jbc.RA117.000567	journal	June 2018
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Induced protein degradation: an emerging drug discovery paradigm Lai, Ashton C.; Crews, Craig M. Nature Reviews Drug Discovery, Vol. 16, Issue 2 https://doi.org/10.1038/nrd.2016.211	journal	November 2016
STATs: transcriptional control and biological impact Levy, David E.; Darnell, J. E. Nature Reviews Molecular Cell Biology, Vol. 3, Issue 9 https://doi.org/10.1038/nrm909	journal	September 2002
P210 and P190 Induce the Tyrosine Phosphorylation and DNA Binding Activity of Multiple Specific STAT Family Members Ilaria, Robert L.; Van Etten, Richard A. Journal of Biological Chemistry, Vol. 271, Issue 49 https://doi.org/10.1074/jbc.271.49.31704	journal	December 1996
FastQ Screen: A tool for multi-genome mapping and quality control Wingett, Steven W.; Andrews, Simon F1000Research, Vol. 7 https://doi.org/10.12688/f1000research.15931.1	journal	January 2018
STAT5 is essential for IL-7–mediated viability, growth, and proliferation of T-cell acute lymphoblastic leukemia cells Ribeiro, Daniel; Melão, Alice; van Boxtel, Ruben Blood Advances, Vol. 2, Issue 17 https://doi.org/10.1182/bloodadvances.2018021063	journal	September 2018
The Molecular Signatures Database Hallmark Gene Set Collection Liberzon, Arthur; Birger, Chet; Thorvaldsdóttir, Helga Cell Systems, Vol. 1, Issue 6 https://doi.org/10.1016/j.cels.2015.12.004	journal	December 2015
Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. Carlesso, N.; Frank, D. A.; Griffin, J. D. The Journal of experimental medicine, Vol. 183, Issue 3 https://doi.org/10.1084/jem.183.3.811	journal	March 1996
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome Li, Bo; Dewey, Colin N. BMC Bioinformatics, Vol. 12, Issue 1 https://doi.org/10.1186/1471-2105-12-323	journal	August 2011
JAK of all trades: JAK2-STAT5 as novel therapeutic targets in BCR-ABL1+ chronic myeloid leukemia Warsch, Wolfgang; Walz, Christoph; Sexl, Veronika Blood, Vol. 122, Issue 13 https://doi.org/10.1182/blood-2013-02-485573	journal	September 2013
Catalytic in vivo protein knockdown by small-molecule PROTACs Bondeson, Daniel P.; Mares, Alina; Smith, Ian E. D. Nature Chemical Biology, Vol. 11, Issue 8 https://doi.org/10.1038/nchembio.1858	journal	June 2015
Essential role for Stat5a/b in myeloproliferative neoplasms induced by BCR-ABL1 and JAK2V617F in mice Walz, Christoph; Ahmed, Wesam; Lazarides, Katherine Blood, Vol. 119, Issue 15 https://doi.org/10.1182/blood-2011-12-397554	journal	April 2012
Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring Jabbour, Elias; Kantarjian, Hagop American Journal of Hematology, Vol. 95, Issue 6 https://doi.org/10.1002/ajh.25792	journal	April 2020
Direct Targeting Options for STAT3 and STAT5 in Cancer Orlova, Anna; Wagner, Christina; de Araujo, Elvin D. Cancers, Vol. 11, Issue 12 https://doi.org/10.3390/cancers11121930	journal	December 2019
Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 6 (STAT6) with Cell-Permeable, Phosphatase-Stable Phosphopeptide Mimics Potently Inhibits Tyr641 Phosphorylation and Transcriptional Activity Mandal, Pijus K.; Morlacchi, Pietro; Knight, J. Morgan Journal of Medicinal Chemistry, Vol. 58, Issue 22 https://doi.org/10.1021/acs.jmedchem.5b01321	journal	November 2015
CIS, a Cytokine Inducible SH2 Protein, Is a Target of the JAK-STAT5 Pathway and Modulates STAT5 Activation Matsumoto, Akira; Masuhara, Masaaki; Mitsui, Kaoru Blood, Vol. 89, Issue 9 https://doi.org/10.1182/blood.V89.9.3148	journal	May 1997
Critical requirement for Stat5 in a mouse model of polycythemia vera Yan, Dongqing; Hutchison, Robert E.; Mohi, Golam Blood, Vol. 119, Issue 15 https://doi.org/10.1182/blood-2011-03-345215	journal	April 2012
High activation of STAT5A drives peripheral T-cell lymphoma and leukemia Maurer, Barbara; Nivarthi, Harini; Wingelhofer, Bettina Haematologica, Vol. 105, Issue 2 https://doi.org/10.3324/haematol.2019.216986	journal	May 2019
FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD–specific STAT5 activation Yoshimoto, Goichi; Miyamoto, Toshihiro; Jabbarzadeh-Tabrizi, Siamak Blood, Vol. 114, Issue 24 https://doi.org/10.1182/blood-2008-12-196055	journal	December 2009
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles Subramanian, A.; Tamayo, P.; Mootha, V. K. Proceedings of the National Academy of Sciences, Vol. 102, Issue 43, p. 15545-15550 https://doi.org/10.1073/pnas.0506580102	journal	September 2005
BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia Hantschel, Oliver; Warsch, Wolfgang; Eckelhart, Eva Nature Chemical Biology, Vol. 8, Issue 3 https://doi.org/10.1038/nchembio.775	journal	January 2012
Signal Transducer and Activator of Transcription (STAT)5 Activation by BCR/ABL Is Dependent on Intact Src Homology (SH)3 and SH2 Domains of BCR/ABL and Is Required for Leukemogenesis Nieborowska-Skorska, Malgorzata; Wasik, Mariusz A.; Slupianek, Artur The Journal of Experimental Medicine, Vol. 189, Issue 8 https://doi.org/10.1084/jem.189.8.1229	journal	April 1999
SD-91 as A Potent and Selective STAT3 Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression Zhou, Haibin; Bai, Longchuan; Xu, Renqi ACS Medicinal Chemistry Letters, Vol. 12, Issue 6 https://doi.org/10.1021/acsmedchemlett.1c00155	journal	May 2021
Three-dimensional structure of the Stat3β homodimer bound to DNA Becker, Stefan; Groner, Bernd; Müller, Christoph W. Nature, Vol. 394, Issue 6689 https://doi.org/10.1038/28101	journal	July 1998
A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo Bai, Longchuan; Zhou, Haibin; Xu, Renqi Cancer Cell, Vol. 36, Issue 5 https://doi.org/10.1016/j.ccell.2019.10.002	journal	November 2019
Identification of Oncostatin M as a STAT5-Dependent Mediator of Bone Marrow Remodeling in KIT D816V-Positive Systemic Mastocytosis Hoermann, Gregor; Cerny-Reiterer, Sabine; Perné, Andrea The American Journal of Pathology, Vol. 178, Issue 5 https://doi.org/10.1016/j.ajpath.2011.01.020	journal	May 2011
STAT5 in Cancer and Immunity Rani, Aradhana; Murphy, John J. Journal of Interferon & Cytokine Research, Vol. 36, Issue 4 https://doi.org/10.1089/jir.2015.0054	journal	April 2016
Cutadapt removes adapter sequences from high-throughput sequencing reads Martin, Marcel EMBnet.journal, Vol. 17, Issue 1 https://doi.org/10.14806/ej.17.1.200	journal	May 2011
The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences Perez-Riverol, Yasset; Bai, Jingwen; Bandla, Chakradhar Nucleic Acids Research, Vol. 50, Issue D1 https://doi.org/10.1093/nar/gkab1038	journal	November 2021
Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3 Peltola, Katriina J.; Paukku, Kirsi; Aho, Teija L. T. Blood, Vol. 103, Issue 10 https://doi.org/10.1182/blood-2003-09-3126	journal	May 2004
Development and optimization of a binding assay for the XIAP BIR3 domain using fluorescence polarization Nikolovska-Coleska, Zaneta; Wang, Renxiao; Fang, Xueliang Analytical Biochemistry, Vol. 332, Issue 2 https://doi.org/10.1016/j.ab.2004.05.055	journal	September 2004
FLT3 mutations in acute myeloid leukemia cell lines Quentmeier, H.; Reinhardt, J.; Zaborski, M. Leukemia, Vol. 17, Issue 1 https://doi.org/10.1038/sj.leu.2402740	journal	January 2003
The IL-2 Receptor Promotes Lymphocyte Proliferation and Induction of the c-myc, bcl-2, and bcl-x Genes Through the trans-Activation Domain of Stat5 Lord, James D.; McIntosh, Bryan C.; Greenberg, Philip D. The Journal of Immunology, Vol. 164, Issue 5 https://doi.org/10.4049/jimmunol.164.5.2533	journal	March 2000
STAR: ultrafast universal RNA-seq aligner Dobin, Alexander; Davis, Carrie A.; Schlesinger, Felix Bioinformatics, Vol. 29, Issue 1 https://doi.org/10.1093/bioinformatics/bts635	journal	October 2012
Stat5 is indispensable for the maintenance of bcr/abl ‐positive leukaemia Hoelbl, Andrea; Schuster, Christian; Kovacic, Boris EMBO Molecular Medicine, Vol. 2, Issue 3 https://doi.org/10.1002/emmm.201000062	journal	March 2010
Pharmacologic inhibition of STAT5 in acute myeloid leukemia Wingelhofer, Bettina; Maurer, Barbara; Heyes, Elizabeth C. Leukemia, Vol. 32, Issue 5 https://doi.org/10.1038/s41375-017-0005-9	journal	February 2018
Crystal Structure of a Tyrosine Phosphorylated STAT-1 Dimer Bound to DNA Chen, Xiaomin; Vinkemeier, Uwe; Zhao, Yanxiang Cell, Vol. 93, Issue 5 https://doi.org/10.1016/S0092-8674(00)81443-9	journal	May 1998
An SH2 domain model of STAT5 in complex with phospho-peptides define “STAT5 Binding Signatures” Gianti, Eleonora; Zauhar, Randy J. Journal of Computer-Aided Molecular Design, Vol. 29, Issue 5 https://doi.org/10.1007/s10822-015-9835-6	journal	March 2015
JAK/STAT signaling in hematological malignancies Vainchenker, W.; Constantinescu, S. N. Oncogene, Vol. 32, Issue 21 https://doi.org/10.1038/onc.2012.347	journal	August 2012
STAT5 signaling is required for the efficient induction and maintenance of CML in mice Ye, Dan; Wolff, Nicholas; Li, Li Blood, Vol. 107, Issue 12 https://doi.org/10.1182/blood-2005-10-4110	journal	June 2006
Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein Zhou, Haibin; Bai, Longchuan; Xu, Renqi Journal of Medicinal Chemistry, Vol. 62, Issue 24 https://doi.org/10.1021/acs.jmedchem.9b01530	journal	November 2019
Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead Bondeson, Daniel P.; Smith, Blake E.; Burslem, George M. Cell Chemical Biology, Vol. 25, Issue 1 https://doi.org/10.1016/j.chembiol.2017.09.010	journal	January 2018
MultiNotch MS3 Enables Accurate, Sensitive, and Multiplexed Detection of Differential Expression across Cancer Cell Line Proteomes McAlister, Graeme C.; Nusinow, David P.; Jedrychowski, Mark P. Analytical Chemistry, Vol. 86, Issue 14 https://doi.org/10.1021/ac502040v	journal	July 2014
Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms Quintás-Cardama, Alfonso; Vaddi, Kris; Liu, Phillip Blood, Vol. 115, Issue 15 https://doi.org/10.1182/blood-2009-04-214957	journal	April 2010
Molecular signatures database (MSigDB) 3.0 Liberzon, A.; Subramanian, A.; Pinchback, R. Bioinformatics, Vol. 27, Issue 12 https://doi.org/10.1093/bioinformatics/btr260	journal	May 2011
Synthesis and evaluation of 2-{[2-(4-hydroxyphenyl)-ethyl]amino}pyrimidine-5-carboxamide derivatives as novel STAT6 inhibitors Nagashima, Shinya; Yokota, Masaki; Nakai, Ei-ichi Bioorganic & Medicinal Chemistry, Vol. 15, Issue 2 https://doi.org/10.1016/j.bmc.2006.10.015	journal	January 2007

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