Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein

[20] Processing of X-ray diffraction data collected in oscillation mode

Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · see citing works

Features and development of Coot

Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. D. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 27,510 · see citing works

<i>Phaser</i> crystallographic software

McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612 · see citing works

<i>MolProbity</i> : all-atom structure validation for macromolecular crystallography

Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115 · see citing works

Development and validation of a genetic algorithm for flexible docking 1 1Edited by F. E. Cohen

Jones, G., Willett, P., Glen, R. C., Leach, A. R., & Taylor, R. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0897 · Cited by 6,763 · see citing works

STATs: transcriptional control and biological impact

Levy, D. E., & Darnell, J. E. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm909 · Cited by 3,201 · see citing works

Targeting the IL-6/JAK/STAT3 signalling axis in cancer

Johnson, D. E., O'Keefe, R. A., & Grandis, J. R. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2018.8 · Cited by 3,110 · see citing works

The STATs of cancer — new molecular targets come of age

Yu, H., & Jove, R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1275 · Cited by 2,278 · see citing works

Induced protein degradation: an emerging drug discovery paradigm

Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486 · see citing works

Medicinal Chemistry and the Molecular Operating Environment (MOE): Application of QSAR and Molecular Docking to Drug Discovery

Vilar, S., Cozza, G., & Moro, S. (2008) · Current Topics in Medicinal Chemistry · doi:10.2174/156802608786786624 · Cited by 1,200 · see citing works

Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide

Fischer, E. S., Böhm, K., Lydeard, J. R., Yang, H., Stadler, M. B., Cavadini, S., Nagel, J., Serluca, F., Acker, V., Lingaraju, G. M., et al. (2014) · Nature · doi:10.1038/nature13527 · Cited by 1,141 · see citing works

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

Lu, J., Qian, Y., Altieri, M., Dong, H., Wang, J., Raina, K., Hines, J., Winkler, J. D., Crew, A. P., Coleman, K., et al. (2015) · Chemistry &amp; Biology · doi:10.1016/j.chembiol.2015.05.009 · Cited by 1,140 · see citing works

Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead

Bondeson, D. P., Smith, B. E., Burslem, G. M., Buhimschi, A. D., Hines, J., Jaime-Figueroa, S., Wang, J., Hamman, B. D., Ishchenko, A., & Crews, C. M. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.09.010 · Cited by 923 · see citing works

Three-dimensional structure of the Stat3β homodimer bound to DNA

Becker, S., Groner, B., & Müller, C. W. (1998) · Nature · doi:10.1038/28101 · Cited by 792 · see citing works

Antisense oligonucleotides: the next frontier for treatment of neurological disorders

Rinaldi, C., & Wood, M. J. A. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.148 · Cited by 788 · see citing works

Small‐Molecule PROTACS: New Approaches to Protein Degradation

Toure, M., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507978 · Cited by 674 · see citing works

A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo

Bai, L., Zhou, H., Xu, R., Zhao, Y., Chinnaswamy, K., McEachern, D., Chen, J., Yang, C.-Y., Liu, Z., Wang, M., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.002 · Cited by 652 · see citing works

Targeted protein degradation: elements of PROTAC design

Paiva, S.-L., & Crews, C. M. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.02.022 · Cited by 586 · see citing works

Targeting the von Hippel-Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1α interaction

Buckley, D. L., Van Molle, I., Gareiss, P. C., Tae, H. S., Michel, J., Noblin, D. J., Jorgensen, W. L., Ciulli, A., & Crews, C. M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja209924v · Cited by 569 · see citing works

AZD9150, a next-generation antisense oligonucleotide inhibitor of <i>STAT3</i> with early evidence of clinical activity in lymphoma and lung cancer

Hong, D., Kurzrock, R., Kim, Y., Woessner, R., Younes, A., Nemunaitis, J., Fowler, N., Zhou, T., Schmidt, J., Jo, M., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac5272 · Cited by 445 · see citing works

Structure-Guided Design and Optimization of Small Molecules Targeting the Protein–Protein Interaction between the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities

Galdeano, C., Gadd, M. S., Soares, P., Scaffidi, S., Molle, I. V., Birced, I., Hewitt, S. H., Dias, D. M. G., & Ciulli, A. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5011258 · Cited by 424 · see citing works

Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression

Zhou, B. N., Hu, J., Xu, F., Chen, Z., Bai, L., Fernández‐Salas, E., Lin, M., Liu, L., Yang, C., Zhao, Y., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01816 · Cited by 373 · see citing works

IC50-to-Ki: a web-based tool for converting IC50 to Ki values for inhibitors of enzyme activity and ligand binding

Cer, R. Z., Mudunuri, U. S., Stephens, R., & Lebeda, F. J. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp253 · Cited by 370 · see citing works

Roles of unphosphorylated STATs in signaling

Yang, J., & Stark, G. R. (2008) · Cell Research · doi:10.1038/cr.2008.41 · Cited by 347 · see citing works

Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression

Li, Y., Yang, J., Aguilar, A., McEachern, D., Przybranowski, S., Liu, L., Yang, C.-Y., Wang, M., Han, X., & Wang, S. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00909 · Cited by 312 · see citing works

Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression

Qin, C., Hu, Y., Zhou, B., Fernandez-Salas, E., Yang, C.-Y., Liu, L., McEachern, D., Przybranowski, S., Wang, M., Stuckey, J., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00506 · Cited by 281 · see citing works

Targeted Protein Degradation by Small Molecules

Bondeson, D. P., & Crews, C. M. (2017) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103507 · Cited by 207 · see citing works

Targeted Degradation of BET Proteins in Triple-Negative Breast Cancer

Bai, L., Zhou, B., Yang, C.-Y., Ji, J., McEachern, D., Przybranowski, S., Jiang, H., Hu, J., Xu, F., Zhao, Y., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2622 · Cited by 199 · see citing works

Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase: Structure–Activity Relationships Leading to the Chemical Probe (2 S ,4 R )-1-(( S )-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy- N -(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298)

Soares, P., Gadd, M. S., Frost, J., Galdeano, C., Ellis, L. C. J., Epemolu, O., Rocha, S., Read, K. D., & Ciulli, A. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00675 · Cited by 180 · see citing works

Two decades of research in discovery of anticancer drugs targeting STAT3, how close are we?

Beebe, J., Liu, J., & Zhang, J. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.06.006 · Cited by 142 · see citing works

Potent and Selective Phosphopeptide Mimetic Prodrugs Targeted to the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 3

Mandal, P. K., Gao, F., Lü, Z., Ren, Z., Ramesh, R., Birtwistle, J. S., Kaluarachchi, K., Chen, X., Bast, R. C., Liao, W. S. ‐., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm2000882 · Cited by 127 · see citing works

Phosphotyrosyl Mimetics in the Development of Signal Transduction Inhibitors

Burke, T. R., & Lee, K. (2003) · Accounts of Chemical Research · doi:10.1021/ar020127o · Cited by 126 · see citing works

Structure-Based Design of Conformationally Constrained, Cell-Permeable STAT3 Inhibitors

Chen, J., Bai, L., Bernard, D., Nikolovska‐Coleska, Z., Gomez, C., Zhang, J., Han, Y., & Wang, S. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml100010j · Cited by 101 · see citing works

Synthesis of Phosphatase-Stable, Cell-Permeable Peptidomimetic Prodrugs That Target the SH2 Domain of Stat3

Mandal, P. K., Liao, W. S. ‐., & McMurray, J. S. (2009) · Organic Letters · doi:10.1021/ol9012662 · Cited by 74 · see citing works

High-Affinity Peptidomimetic Inhibitors of the DCN1-UBC12 Protein–Protein Interaction

Zhou, H., Zhou, W., Zhou, B. N., Liu, L., Chern, T., Chinnaswamy, K., Lü, J., Bernard, D., Yang, C., Li, S., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01455 · Cited by 70 · see citing works

Conformationally Constrained Peptidomimetic Inhibitors of Signal Transducer and Activator of Transcription 3: Evaluation and Molecular Modeling

Mandal, P. K., Limbrick, D., Coleman, D. R., Dyer, G. A., Ren, Z., Birtwistle, J. S., Xiong, C., Chen, X., Briggs, J. M., & McMurray, J. S. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801491w · Cited by 58 · see citing works

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, P. K., Morlacchi, P., Knight, J. M., Link, T. M., Lee, G. R., Nurieva, R., Singh, D., Dhanik, A., Kavraki, L. E., Corry, D. B., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01321 · Cited by 47 · see citing works

Surface Probing by Fragment-Based Screening and Computational Methods Identifies Ligandable Pockets on the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase

Lucas, X., Molle, I. V., & Ciulli, A. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00842 · Cited by 44 · see citing works

Preparation and application of antibodies to phosphoamino acid sequences

Sun, T., Campbell, M. L., Gordon, W., & Arlinghaus, R. B. (2001) · Biopolymers · doi:10.1002/1097-0282(2001)60:1 · Cited by 28 · see citing works

Design and synthesis of a 1,5-diazabicyclo[6,3,0] dodecane amino acid derivative as a novel dipeptide reverse-turn mimetic

Peng, Y., Sun, H., & Wang, S. (2006) · Tetrahedron Letters · doi:10.1016/j.tetlet.2006.04.053 · Cited by 12 · see citing works

Targeted protein degradation: mechanisms, strategies and application

Zhao, L., Zhao, J., Zhong, K., Tong, A., & Jia, D. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00966-4 · Cited by 986 · see citing works

PROTACs: past, present and future

Li, K., & Crews, C. M. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00193d · Cited by 869 · see citing works

Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy

Li, X., & Song, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00885-3 · Cited by 550 · see citing works

Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer

Ouyang, S., Li, H., Lou, L., Huang, Q., Zhang, Z., Mo, J., Li, M., Lu, J., Zhu, K., Chu, Y., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102317 · Cited by 507 · see citing works

Current strategies for the design of PROTAC linkers: a critical review

Troup, R. I., Fallan, C., & Baud, M. G. J. (2020) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2020.00018 · Cited by 424 · see citing works

Chemistries of bifunctional PROTAC degraders

Cao, C., He, M., Wang, L., He, Y., & Rao, Y. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00220e · Cited by 313 · see citing works

PROTAC: An Effective Targeted Protein Degradation Strategy for Cancer Therapy

Qi, S., Dong, J., Xu, Z., Cheng, X., Zhang, W., & Qin, J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.692574 · Cited by 299 · see citing works

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

He, M., Cao, C., Ni, Z., Liu, Y., Song, P., Hao, S., He, Y., Sun, X., & Rao, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00999-9 · Cited by 283 · see citing works

Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges

Zeng, S., Huang, W., Zheng, X., Cheng, L., Zhang, Z., Wang, J., & Shen, Z. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112981 · Cited by 262 · see citing works

Unraveling the Role of Linker Design in Proteolysis Targeting Chimeras

Bemis, T. A., Clair, J. J. L., & Burkart, M. D. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00482 · Cited by 244 · see citing works

PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics

Khan, S., He, Y., Zhang, X., Yuan, Y., Pu, S., Kong, Q., Zheng, G., & Zhou, D. (2020) · Oncogene · doi:10.1038/s41388-020-1336-y · Cited by 252 · see citing works

Recent Update on Development of Small-Molecule STAT3 Inhibitors for Cancer Therapy: From Phosphorylation Inhibition to Protein Degradation

Dong, J., Cheng, X.-D., Zhang, W.-D., & Qin, J.-J. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00629 · Cited by 232 · see citing works

A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK/STAT targeting in T-cell lymphomas

Moskowitz, A. J., Ghione, P., Jacobsen, E. D., Ruan, J., Schatz, J. H., Noor, S. J., Myskowski, P. L., Vardhana, S. A., Ganesan, N., Hancock, H., et al. (2021) · Blood · doi:10.1182/blood.2021013379 · Cited by 192 · see citing works

PROTACs to address the challenges facing small molecule inhibitors

Martín-Acosta, P., & Xiao, X. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112993 · Cited by 186 · see citing works

E3 ligase ligand chemistries: from building blocks to protein degraders

Sosič, I., Bricelj, A., & Steinebach, C. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00148a · Cited by 173 · see citing works

Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein

Wang, M., Lu, J., Wang, M., Yang, C.-Y., & Wang, S. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00471 · Cited by 172 · see citing works

The state of the art of PROTAC technologies for drug discovery

Wang, C., Zheng, C., Wang, H., Zhang, L., Liu, Z., & Xu, P. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114290 · Cited by 129 · see citing works

Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies

He, Y., Khan, S., Huo, Z., Lv, D., Zhang, X., Liu, X., Yuan, Y., Hromas, R., Xu, M., Zheng, G., et al. (2020) · Journal of Hematology &amp; Oncology · doi:10.1186/s13045-020-00924-z · Cited by 126 · see citing works

Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity

Zhang, X., Thummuri, D., Liu, X., Hu, W., Zhang, P., Khan, S., Yuan, Y., Zhou, D., & Zheng, G. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112186 · Cited by 123 · see citing works

Targeted protein degrader development for cancer: advances, challenges, and opportunities

Fang, Y., Wang, S., Han, S., Zhao, Y., Yu, C., Liu, H., & Li, N. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.03.003 · Cited by 110 · see citing works

Targeting the undruggables—the power of protein degraders

Zhang, C., Liu, Y., Li, G., Yang, Z., Han, C., Sun, X., Sheng, C., Ding, K., & Rao, Y. (2024) · 中国科学通报：英文版 · doi:10.1016/j.scib.2024.03.056 · Cited by 108 · see citing works

STAT3: Versatile Functions in Non-Small Cell Lung Cancer

Mohrherr, J., Uras, I. Z., Moll, H. P., & Casanova, E. (2020) · Cancers · doi:10.3390/cancers12051107 · Cited by 106 · see citing works

Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13

Yang, J., Chang, Y., Tien, J. C.-Y., Wang, Z., Zhou, Y., Zhang, P., Huang, W., Vo, J. N., Apel, I. J., Wang, C., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00384 · Cited by 96 · see citing works

DYRK1A regulates B cell acute lymphoblastic leukemia through phosphorylation of FOXO1 and STAT3

Bhansali, R. S., Rammohan, M., Lee, P., Laurent, A. P., Wen, Q., Suraneni, P. K., Yip, B. H., Tsai, Y.-C., Jenni, S., Bornhauser, B. C., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci135937 · Cited by 92 · see citing works

Targeting NRF2 to treat cancer

Sivinski, J., Zhang, D. D., & Chapman, E. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.06.003 · Cited by 90 · see citing works

Strategies for the discovery of oral PROTAC degraders aimed at cancer therapy

Han, X., & Sun, Y. (2022) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2022.101062 · Cited by 89 · see citing works

Discovery of an orally active VHL-recruiting PROTAC that achieves robust HMGCR degradation and potent hypolipidemic activity in vivo

Luo, G., Li, Z., Lin, X., Li, X., Chen, Y., Xi, K., Xiao, M., Wei, H., Zhu, L., & Xiang, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.11.001 · Cited by 83 · see citing works

Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors

LaPlante, G., & Zhang, W. (2021) · Cancers · doi:10.3390/cancers13123079 · Cited by 82 · see citing works

Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders

Yang, X., Wang, Z., Pei, Y., Song, N., Xu, L., Feng, B., Wang, H., Luo, X., Hu, X., Qiu, X., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113341 · Cited by 85 · see citing works

Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia

Chang, Y., Min, J., Jarusiewicz, J., Actis, M., Bradford, S. Y. C., Mayasundari, A., Yang, L., Chepyala, D., Alcock, L. J., Roberts, K. G., et al. (2021) · Blood · doi:10.1182/blood.2020006846 · Cited by 79 · see citing works

Druggable genome and precision medicine in cancer: current challenges

Dupont, C., Riegel, K., Pompaiah, M., Juhl, H. H., & Rajalingam, K. (2021) · FEBS Journal · doi:10.1111/febs.15788 · Cited by 78 · see citing works

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

Kaneshige, A., Bai, L., Wang, M., McEachern, D., Meagher, J. L., Xu, R., Wang, Y., Jiang, W., Metwally, H., Kirchhoff, P. D., et al. (2023) · Nature Chemical Biology · doi:10.1038/s41589-022-01248-4 · Cited by 73 · see citing works

Deregulated transcription factors in cancer cell metabolisms and reprogramming

Kant, R., Manne, R., Anas, M., Penugurti, V., Chen, T., Pan, B., Hsu, C.-C., & Lin, H. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.10.001 · Cited by 72 · see citing works

Computer-Aided Drug Discovery for Undruggable Targets

Sun, Q., Wang, H., Xie, J., Wang, L., Mu, J., Li, J., Ren, Y., & Lai, L. (2025) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00969 · Cited by 69 · see citing works

PROTACs: A novel strategy for cancer drug discovery and development

Han, X., & Sun, Y. (2023) · MedComm · doi:10.1002/mco2.290 · Cited by 67 · see citing works

Targeted Protein Degradation: Advances, Challenges, and Prospects for Computational Methods

Mostofian, B., Martin, H., Razavi, A. M., Patel, S., Allen, B. K., Sherman, W., & Izaguirre, J. A. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c00603 · Cited by 68 · see citing works

PROTAC degraders with ligands recruiting MDM2 E3 ubiquitin ligase: an updated perspective

Han, X., Wei, W., & Sun, Y. (2022) · Acta Materia Medica · doi:10.15212/amm-2022-0010 · Cited by 67 · see citing works

Targeting androgen receptor degradation with PROTACs from bench to bedside

Jia, X., & Han, X. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114112 · Cited by 67 · see citing works

The rise of degrader drugs

Teng, M., & Gray, N. S. (2023) · Cell chemical biology · doi:10.1016/j.chembiol.2023.06.020 · Cited by 67 · see citing works

Targeted protein degradation in cancers: Orthodox PROTACs and beyond

Li, J., Chen, X., Lü, A., & Liang, C. (2023) · The Innovation · doi:10.1016/j.xinn.2023.100413 · Cited by 66 · see citing works

Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91

Hanafi, M., Chen, X., & Neamati, N. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01897 · Cited by 61 · see citing works

E3 ligase ligand optimization of Clinical PROTACs

Jiang, H., Xiong, H., Gu, S.-X., & Wang, M. (2023) · Frontiers in Chemistry · doi:10.3389/fchem.2023.1098331 · Cited by 61 · see citing works

Discovery of Exceptionally Potent, Selective, and Efficacious PROTAC Degraders of CBP and p300 Proteins

Thomas, J. E., Wang, M., Jiang, W., Wang, M., Wang, L., Wen, B., Sun, D., & Wang, S. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00492 · Cited by 61 · see citing works

Discovery of a PROTAC targeting ALK with in vivo activity

Yan, G., Zhong, X.-X., Lin, Y., Pu, C., Shan, H., Lan, S., Zhou, M., Hou, X., Yang, J., & Li, R. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.113150 · Cited by 59 · see citing works

Taking Aim at the Undruggable

Coleman, N., & Rodon, J. A. (2021) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_325885 · Cited by 58 · see citing works

Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer

Jin, J., Wu, Y., Zhao, Z., Wu, Y., Zhou, Y.-D., Liu, S., Sun, Q., Yang, G., Lin, J., Nagle, D. G., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.160606 · Cited by 57 · see citing works

Optimization of PROTAC Ternary Complex Using DNA Encoded Library Approach

Chen, Q., Liu, C., Wang, W., Meng, X., Cheng, X., Li, X.-Y., Cai, L., Luo, L., He, X., Qu, H., et al. (2023) · ACS Chemical Biology · doi:10.1021/acschembio.2c00797 · Cited by 55 · see citing works

SD-91 as A Potent and Selective STAT3 Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression

Zhou, H., Bai, L., Xu, R., McEachern, D., Chinnaswamy, K., Li, R., Wen, B., Wang, M., Yang, C., Meagher, J. L., et al. (2021) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.1c00155 · Cited by 56 · see citing works

Nucleic-Acid-Based Targeted Degradation in Drug Discovery

Wang, W., He, S., Dong, G., & Sheng, C. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00875 · Cited by 55 · see citing works

Discovery of STAT3 Inhibitors: Recent Advances and Future Perspectives

Song, J., Wang, J., Tian, S., & Li, H. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867329666220819093117 · Cited by 54 · see citing works

Unlocking the potential of PROTACs: A comprehensive review of protein degradation strategies in disease therapy

Bhole, R. P., Kute, P. R., Chikhale, R. V., Bonde, C. G., Pant, A. M., & Gurav, S. S. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106720 · Cited by 48 · see citing works

AZD5438-PROTAC: A selective CDK2 degrader that protects against cisplatin- and noise-induced hearing loss

Hati, S., Zallocchi, M., Hazlitt, R. A., Li, Y., Vijayakumar, S., Min, J., Ranković, Z., Lovas, S., & Zuo, J. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113849 · Cited by 46 · see citing works

Selectivity through Targeted Protein Degradation (TPD)

Gopalsamy, A. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00397 · Cited by 46 · see citing works

Digesting the Role of JAK-STAT and Cytokine Signaling in Oral and Gastric Cancers

Ni, Y., Low, J. T., Silke, J., & O’Reilly, L. A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.835997 · Cited by 46 · see citing works

Discovery of a Potent and Selective STAT5 PROTAC Degrader with Strong Antitumor Activity In Vivo in Acute Myeloid Leukemia

Kaneshige, A., Bai, L., Wang, M., McEachern, D., Meagher, J. L., Xu, R., Kirchhoff, P. D., Wen, B., Sun, D., Stuckey, J. A., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01665 · Cited by 46 · see citing works

Small molecule drug discovery targeting the JAK-STAT pathway

Lv, Y., Mi, P., Babon, J. J., Fan, G.-H., Qi, J., Cao, L., Lang, J., Zhang, J., Wang, F., & Kobe, B. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107217 · Cited by 46 · see citing works

Targeting the STAT3 pathway with STAT3 degraders

Wang, Z., Liao, X., He, H., Guo, X., & Chen, J. (2024) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2024.07.003 · Cited by 46 · see citing works

Proteases and Their Modulators in Cancer Therapy: Challenges and Opportunities

Song, R., Qiao, W., He, J., Huang, J., Luo, Y., & Yang, T. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01640 · Cited by 45 · see citing works

Targeting key proteins involved in transcriptional regulation for cancer therapy: Current strategies and future prospective

Pei, H., Guo, W., Peng, Y., Xiong, H., & Chen, Y. (2022) · Medicinal Research Reviews · doi:10.1002/med.21886 · Cited by 45 · see citing works

Selective JAK1 inhibitors for the treatment of inflammatory bowel disease

Nielsen, O. H., Boye, T. L., Gubatan, J. M. B., Chakravarti, D., Jaquith, J. B., & LaCasse, E. C. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108402 · Cited by 44 · see citing works

Advances and perspectives of proteolysis targeting chimeras (PROTACs) in drug discovery

Xi, J., Zhang, R., Chen, K., Yao, L., Li, M., Jiang, R., Li, X., & Fan, L. (2022) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2022.105848 · Cited by 45 · see citing works

PROTACs: New method to degrade transcription regulating proteins

Hu, B.-C., Zhou, Y., Sun, D., Yang, Y., Liu, Y., Li, X., Li, H., & Chen, L. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112698 · Cited by 43 · see citing works

Discovery of Novel Azetidine Amides as Potent Small-Molecule STAT3 Inhibitors

Brotherton‐Pleiss, C., Yue, P., Zhu, Y., Nakamura, K., Chen, W., Fu, W., Kubota, C. S., Chen, J., Alonso-Valenteen, F., Mikhael, S., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01705 · Cited by 43 · see citing works

Emerging Pharmacotherapeutic Strategies to Overcome Undruggable Proteins in Cancer

Lu, Y., Yang, Y., Zhu, G., Zeng, H., Fan, Y., Guo, F., Xu, D., Wang, B., Chen, D., & Ge, G. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.83026 · Cited by 41 · see citing works

Journey of Von Hippel-Lindau (VHL) E3 ligase in PROTACs design: From VHL ligands to VHL-based degraders

Setia, N., Almuqdadi, H. T. A., & Abid, M. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.116041 · Cited by 41 · see citing works

Recent advances in the development of allosteric protein tyrosine phosphatase inhibitors for drug discovery

Elhassan, R. M., Hou, X., & Fang, H. (2021) · Medicinal Research Reviews · doi:10.1002/med.21871 · Cited by 41 · see citing works

Cereblon-Recruiting PROTACs: Will New Drugs Have to Face Old Challenges?

Cieślak, M., & Słowianek, M. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15030812 · Cited by 41 · see citing works

Protein degradation: a novel computational approach to design protein degrader probes for main protease of SARS-CoV-2

Shaheer, M., Singh, R., & Sobhia, M. E. (2021) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2021.1953601 · Cited by 40 · see citing works

Small molecular inhibitors and degraders targeting STAT3 for cancer therapy: An updated review (from 2022 to 2024)

Kang, Z., Shen, L., Li, Y., Song, J., Peng, Y., & Chen, Y. (2024) · Chinese Chemical Letters · doi:10.1016/j.cclet.2024.110447 · Cited by 39 · see citing works

Targeting the Undruggable: Recent Progress in PROTAC-Induced Transcription Factor Degradation

Jung, H., & Lee, Y. (2025) · Cancers · doi:10.3390/cancers17111871 · Cited by 39 · see citing works

Proteolysis‐Targeting Chimera (PROTAC): Current Applications and Future Directions

Fan, G., Chen, S., Zhang, Q., Yu, N., Shen, Z., Liu, Z., Guo, W., Tang, Z., Yang, J., & Liu, M. (2025) · MedComm · doi:10.1002/mco2.70401 · Cited by 44 · see citing works

Targeting SHP2 as a therapeutic strategy for inflammatory diseases

Liu, Y., Yang, X., Wang, Y., Yang, Y., Sun, D., Li, H., & Chen, L. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113264 · Cited by 40 · see citing works

PROTACs, molecular glues and bifunctionals from bench to bedside: Unlocking the clinical potential of catalytic drugs

Maneiro, M., Vita, E. D., Conole, D., Kounde, C. S., Zhang, Q., & Tate, E. W. (2021) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2021.01.002 · Cited by 38 · see citing works

New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy

Zeng, L., Zhu, Y., Moreno, C. S., & Wan, Y. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.02.003 · Cited by 37 · see citing works

Light-Controllable PROTACs for Temporospatial Control of Protein Degradation

Liu, J., Peng, Y., & Wei, W. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.678077 · Cited by 38 · see citing works

Oligo-PROTAC strategy for cell-selective and targeted degradation of activated STAT3

Hall, J., Zhang, Z., Bhattacharya, S., Wang, D., Alcantara, M. B., Liang, Y., Swiderski, P. M., Forman, S. J., Kwak, L. W., Vaidehi, N., et al. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102137 · Cited by 38 · see citing works

Targeted Protein Degradation (TPD) for Immunotherapy: Understanding Proteolysis Targeting Chimera-Driven Ubiquitin-Proteasome Interactions

Kamaraj, R., Ghosh, S., Das, S., Sen, S., Kumar, P. R., Majumdar, M., Dasgupta, R., Mukherjee, S., Das, S., Ghose, I., et al. (2024) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.4c00253 · Cited by 37 · see citing works

Targeted protein degradation: current molecular targets, localization, and strategies

Pliatsika, D., Blatter, C., & Riedl, R. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.104178 · Cited by 37 · see citing works

Targeted Protein Degradation: Design Considerations for PROTAC Development

Tran, N. L., Leconte, G. A., & Ferguson, F. M. (2022) · Current Protocols · doi:10.1002/cpz1.611 · Cited by 34 · see citing works

Precise Conformational Control Yielding Highly Potent and Exceptionally Selective BRD4 Degraders with Strong Antitumor Activity

Hu, J., Hu, B., Xu, F., Wang, M., Qin, C., McEachern, D., Stuckey, J. A., & Wang, S. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00520 · Cited by 35 · see citing works

Discovery of a Highly Potent and Orally Bioavailable STAT3 Dual Phosphorylation Inhibitor for Pancreatic Cancer Treatment

He, P., Bian, A., Miao, Y., Jin, W., Chen, H., He, J., Li, L., Sun, Y., Ye, J., Liu, M., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01554 · Cited by 34 · see citing works

Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes

Dankner, M., Maritan, S. M., Priego, N., Kruck, G., Nkili-Meyong, A. A., Nadaf, J., Zhuang, R., Annis, M. G., Zuo, D., Nowakowski, A., et al. (2024) · Neuro-Oncology · doi:10.1093/neuonc/noae013 · Cited by 34 · see citing works

The Ubiquitin–Proteasome System in Tumor Metabolism

Wang, J., Xiang, Y., Fan, M., Fang, S., & Hua, Q. (2023) · Cancers · doi:10.3390/cancers15082385 · Cited by 31 · see citing works

Design and optimization strategies of PROTACs and its Application, Comparisons to other targeted protein degradation for multiple oncology therapies

Malarvannan, M., Unnikrishnan, S., Monohar, S., Ravichandiran, V., & Paul, D. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.107984 · Cited by 33 · see citing works

Targeting STAT3 with Proteolysis Targeting Chimeras and Next-Generation Antisense Oligonucleotides

Shiah, J. V., Grandis, J. R., & Johnson, D. E. (2020) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0599 · Cited by 32 · see citing works

A chemical probe inhibitor targeting STAT1 restricts cancer stem cell traits and angiogenesis in colorectal cancer

Chou, P.-H., Luo, C.-K., Wali, N., Lin, W.-Y., Ng, S.-K., Wang, C., Zhao, M., Lin, S., Yang, P., Liu, P.-J., et al. (2022) · Journal of Biomedical Science · doi:10.1186/s12929-022-00803-4 · Cited by 32 · see citing works

Discovery of SD-436: A Potent, Highly Selective and Efficacious STAT3 PROTAC Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression

Xu, R., Zhou, H., Bai, L., McEachern, D., Wu, D., Acharyya, R. K., Wang, M., Tošović, J., Yang, C., Chinnaswamy, K., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01946 · Cited by 31 · see citing works

Palladium-catalyzed [4 + 3] dearomatizing cycloaddition reaction of N -iminoquinolinium ylides

Dai, W., Li, C., Liu, Y., Han, X., Li, X., Chen, K., & Liu, H. S. (2020) · Organic Chemistry Frontiers · doi:10.1039/d0qo00320d · Cited by 31 · see citing works

Recent advances in synthetic and medicinal chemistry of phosphotyrosine and phosphonate-based phosphotyrosine analogues

Makukhin, N., & Ciulli, A. (2020) · RSC Medicinal Chemistry · doi:10.1039/d0md00272k · Cited by 31 · see citing works

Altered pathways and targeted therapy in double hit lymphoma

Zhuang, Y., Che, J., Wu, M., Guo, Y. L., Xu, Y., Dong, X., & Yang, H. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01249-9 · Cited by 30 · see citing works

Discovery of 2-Amino-3-cyanothiophene Derivatives as Potent STAT3 Inhibitors for the Treatment of Osteosarcoma Growth and Metastasis

Jin, W., Zhang, T., Zhou, W., He, P., Sun, Y., Hu, S., Chen, H., Ma, X., Peng, Y., Yi, Z., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00004 · Cited by 30 · see citing works

Progress of small molecules for targeted protein degradation: PROTACs and other technologies

Zhao, H., Xin, M., & Zhang, S. (2023) · Drug Development Research · doi:10.1002/ddr.22026 · Cited by 31 · see citing works

Discovery of novel BCL6-Targeting PROTACs with effective antitumor activities against DLBCL in vitro and in vivo

Mi, D., Cheng, L., Li, Y., Yao, M., Li, Y., Hong, K., Xie, C., & Chen, Y. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116789 · Cited by 29 · see citing works

Discovery of AK-1690: A Potent and Highly Selective STAT6 PROTAC Degrader

Kaneshige, A., Yang, Y., Bai, L., Wang, M., Xu, R., Mallik, L., Chinnaswamy, K., Metwally, H., Wang, Y., McEachern, D., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01009 · Cited by 29 · see citing works

Design, synthesis and biological evaluation of novel potent STAT3 inhibitors based on BBI608 for cancer therapy

Feng, K.-R., Wang, F., Shi, X., Tan, Y., Zhao, J., Zhang, J., Li, Q., Lin, G., Gao, D., & Tian, P. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112428 · Cited by 29 · see citing works

Small-Molecule PROTACs for Cancer Immunotherapy

Liu, Z., Zhang, Y., Xiang, Y., & Kang, X. (2022) · Molecules · doi:10.3390/molecules27175439 · Cited by 29 · see citing works

Discovery of a Novel Potent STAT3 Inhibitor HP590 with Dual p-Tyr705/Ser727 Inhibitory Activity for Gastric Cancer Treatment

He, P., Miao, Y., Sun, Y., Bian, A., Jin, W., Chen, H., Ye, J., He, J., Peng, Y., Gu, H., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00413 · Cited by 29 · see citing works

The new direction of drug development: Degradation of undruggable targets through targeting chimera technology

Liang, X., Ren, H., Han, F., Liang, R., Zhao, J., & Liu, H. S. (2023) · Medicinal Research Reviews · doi:10.1002/med.21992 · Cited by 28 · see citing works

The application of ubiquitin ligases in the PROTAC drug design

Chen, Y., & Jin, J. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa053 · Cited by 28 · see citing works

Photopharmacology of Proteolysis-Targeting Chimeras: A New Frontier for Drug Discovery

Zeng, S., Zhang, H., Shen, Z., & Huang, W. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.639176 · Cited by 27 · see citing works

Discovery of SD-2301 as a Highly Potent and Selective PROTAC STAT3 Degrader Capable of Achieving Complete Tumor Regression with Single Administration

Acharyya, R. K., Bai, L., Zhou, H., Wu, D., Wang, M., Metwally, H., McEachern, D., Wang, M., Wen, B., Sun, D., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00743 · Cited by 1 · see citing works

Discovery of SD-436: A Potent, Highly Selective and Efficacious STAT3 PROTAC Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression

Xu, R., Zhou, H., Bai, L., McEachern, D., Wu, D., Acharyya, R. K., Wang, M., Tošović, J., Yang, C., Chinnaswamy, K., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01946 · Cited by 31 · see citing works

Abstract 4519: Discovery of highly potent, selective and efficacious STAT3 PROTAC degraders capable of achieving complete tumor regression

Zhou, H., Wu, D., Bai, L., Acharyya, R. K., Metwally, H., McEachern, D., Wen, B., Sun, D., & Wang, S. (2024) · Cancer Research · doi:10.1158/1538-7445.am2024-4519

Abstract 3881: Discovery of highly potent, selective and efficacious STAT3 PROTAC degraders capable of achieving long-lasting tumor regression

Zhou, H., Wu, D., Bai, L., Acharyya, R. K., Metwally, H., McEachern, D., Wen, B., Sun, D., & Wang, S. (2024) · Cancer Research · doi:10.1158/1538-7445.am2024-3881 · Cited by 1 · see citing works

Discovery of SD-965 as a Potent, Selective, and Efficacious STAT3 PROTAC Degrader

Wu, D., Zhou, H., Bai, L., Acharyya, R. K., Metwally, H., McEachern, D., Wang, M., Tošović, J., Rej, R. K., Wang, M., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c03767