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Development of Stabilized Peptide-Based PROTACs against Estrogen Receptor α

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    Development of Stabilized Peptide-Based PROTACs against Estrogen Receptor α
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    • Yanhong Jiang
      Yanhong Jiang
      Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
      More by Yanhong Jiang
      Orcidhttp://orcid.org/0000-0003-4366-0503
    • Qiwen Deng
      Qiwen Deng
      Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
      More by Qiwen Deng
    • Hui Zhao
      Hui Zhao
      Division of Life Sciences, Clarivate Analytics, Beijing, 100190, China
      More by Hui Zhao
    • Mingsheng Xie
      Mingsheng Xie
      Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
      More by Mingsheng Xie
    • Longjian Chen
      Longjian Chen
      Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
      More by Longjian Chen
    • Feng Yin
      Feng Yin
      Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
      More by Feng Yin
    • Xuan Qin
      Xuan Qin
      Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
      More by Xuan Qin
    • Weihao Zheng
      Weihao Zheng
      Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
      More by Weihao Zheng
    • Yongjuan Zhao*
      Yongjuan Zhao
      Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
      *E-mail: [email protected]
      More by Yongjuan Zhao
    • Zigang Li*
      Zigang Li
      Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
      *E-mail: [email protected]
      More by Zigang Li
      Orcidhttp://orcid.org/0000-0002-3630-8520
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    ACS Chemical Biology

    Cite this: ACS Chem. Biol. 2018, 13, 3, 628–635
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    https://doi.org/10.1021/acschembio.7b00985
    Published December 22, 2017
    Copyright © 2017 American Chemical Society
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    Abstract

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    Peptide modulators targeting protein–protein interactions (PPIs) exhibit greater potential than small-molecule drugs in several important aspects including facile modification and relative large contact surface area. Stabilized peptides constructed by variable chemistry methods exhibit improved peptide stability and cell permeability compared to that of the linears. Herein, we designed a stabilized peptide-based proteolysis-targeting chimera (PROTAC) targeting estrogen receptor α (ERα) by tethering an N-terminal aspartic acid cross-linked stabilized peptide ERα modulator (TD-PERM) with a pentapeptide that binds the Von Hippel–Lindau (VHL) E3 ubiquitin ligase complex. The resulting heterobifunctional peptide (TD-PROTAC) selectively recruits ERα to the VHL E3 ligase complex, leading to the degradation of ERα in a proteasome-dependent manner. Compared with the control peptides, TD-PROTAC shows significantly enhanced activities in reducing the transcription of the ERα-downstream genes and inhibiting the proliferation of ERα-positive breast cancer cells. In addition, in vivo experiments indicate that TD-PROTAC leads to tumor regression in the MCF-7 mouse xenograft model. This work is a successful attempt to construct PROTACs based on cell-permeable stabilized peptides, which significantly broadens the chemical space of PROTACs and stabilized peptides.

    Copyright © 2017 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acschembio.7b00985.

    • Figures S1–S6, Tables S1–S3, and HPLC traces and MS spectra of synthesized peptides (PDF)

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    2. Colin S. Swenson, Gunasheil Mandava, Deborah M. Thomas, Raymond E. Moellering. Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics. Chemical Reviews 2024, 124 (22) , 13020-13093. https://doi.org/10.1021/acs.chemrev.4c00423
    3. Ranjan Kumar Acharyya, Rohan Kalyan Rej, Biao Hu, Zhixiang Chen, Dimin Wu, Jianfeng Lu, Hoda Metwally, Donna McEachern, Yu Wang, Wei Jiang, Longchuan Bai, Jelena Tošović, Christina L. Gersch, Guozhang Xu, Weihong Zhang, WenXue Wu, E. Scott Priestley, Zhihua Sui, Farzad Sarkari, Bo Wen, Duxin Sun, James M. Rae, Shaomeng Wang. Discovery of ERD-1233 as a Potent and Orally Efficacious Estrogen Receptor PROTAC Degrader for the Treatment of ER+ Human Breast Cancer. Journal of Medicinal Chemistry 2024, 67 (21) , 19010-19037. https://doi.org/10.1021/acs.jmedchem.4c01521
    4. Matthew K. Whittaker, George N. Bendzunas, Mahsa Shirani, Timothy J. LeClair, Bassem Shebl, Taylor C. Dill, Philip Coffino, Sanford M. Simon, Eileen J. Kennedy. Targeted Degradation of Protein Kinase A via a Stapled Peptide PROTAC. ACS Chemical Biology 2024, 19 (9) , 1888-1895. https://doi.org/10.1021/acschembio.4c00237
    5. Tae-Kyung Lee, Kara Kassees, Chia-Yuan Chen, Suryavathi Viswanadhapalli, Karla Parra, Ratna K. Vadlamudi, Jung-Mo Ahn. Structure–Activity Relationship Study of Tris-Benzamides as Estrogen Receptor Coregulator Binding Modulators. ACS Pharmacology & Translational Science 2024, 7 (7) , 2023-2043. https://doi.org/10.1021/acsptsci.4c00125
    6. Bohan Ma, Donghua Liu, Mengjun Zheng, Zhe Wang, Dize Zhang, Yanlin Jian, Jian Ma, Yizeng Fan, Yule Chen, Yang Gao, Jing Liu, Xiang Li, Lei Li. Development of a Double-Stapled Peptide Stabilizing Both α-Helix and β-Sheet Structures for Degrading Transcription Factor AR-V7. JACS Au 2024, 4 (2) , 816-827. https://doi.org/10.1021/jacsau.3c00795
    7. Chuan Wan, Yichi Zhang, Jinpeng Wang, Yun Xing, Dongyan Yang, Qinhong Luo, Jianbo Liu, Yuxin Ye, Zhihong Liu, Feng Yin, Rui Wang, Zigang Li. Traceless Peptide and Protein Modification via Rational Tuning of Pyridiniums. Journal of the American Chemical Society 2024, 146 (4) , 2624-2633. https://doi.org/10.1021/jacs.3c11864
    8. Baohua Xie, Zhinang Yin, Zhiye Hu, Junhui Lv, Chuanqian Du, Xiangping Deng, Yuan Huang, Qiuzi Li, Jian Huang, Kaiwei Liang, Hai-Bing Zhou, Chune Dong. Discovery of a Novel Class of PROTACs as Potent and Selective Estrogen Receptor α Degraders to Overcome Endocrine-Resistant Breast Cancer In Vitro and In Vivo. Journal of Medicinal Chemistry 2023, 66 (10) , 6631-6651. https://doi.org/10.1021/acs.jmedchem.2c02032
    9. Xinyan Zhang, Zhilin Zhang, Xiaoqi Xue, Tingting Fan, Chunyan Tan, Feng Liu, Ying Tan, Yuyang Jiang. PROTAC Degrader of Estrogen Receptor α Targeting DNA-Binding Domain in Breast Cancer. ACS Pharmacology & Translational Science 2022, 5 (11) , 1109-1118. https://doi.org/10.1021/acsptsci.2c00109
    10. Chuan Dai, Chenshan Lian, Huilong Fang, Qinhong Luo, Junrong Huang, Min Yang, Heng Yang, Lizhi Zhu, Jinqiang Zhang, Feng Yin, Zigang Li. Diversity-Oriented Synthesis of ERα Modulators via Mitsunobu Macrocyclization. Organic Letters 2022, 24 (19) , 3532-3537. https://doi.org/10.1021/acs.orglett.2c01239
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    12. Xiang Li, Si Chen, Wei-Dong Zhang, Hong-Gang Hu. Stapled Helical Peptides Bearing Different Anchoring Residues. Chemical Reviews 2020, 120 (18) , 10079-10144. https://doi.org/10.1021/acs.chemrev.0c00532
    13. Brett L. Roberts, Zhi-Xiong Ma, Ang Gao, Eric D. Leisten, Dan Yin, Wei Xu, Weiping Tang. Two-Stage Strategy for Development of Proteolysis Targeting Chimeras and its Application for Estrogen Receptor Degraders. ACS Chemical Biology 2020, 15 (6) , 1487-1496. https://doi.org/10.1021/acschembio.0c00140
    14. Sayumi Yamazoe, Jeffrey Tom, Yue Fu, Wenqiong Wu, Liang Zeng, Changlei Sun, Qi Liu, Jie Lin, Kui Lin, Wayne J. Fairbrother, Steven T. Staben. Heterobifunctional Molecules Induce Dephosphorylation of Kinases–A Proof of Concept Study. Journal of Medicinal Chemistry 2020, 63 (6) , 2807-2813. https://doi.org/10.1021/acs.jmedchem.9b01167
    15. Jiantao Hu, Biao Hu, Mingliang Wang, Fuming Xu, Bukeyan Miao, Chao-Yie Yang, Mi Wang, Zhaomin Liu, Daniel F. Hayes, Krishnapriya Chinnaswamy, James Delproposto, Jeanne Stuckey, Shaomeng Wang. Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER). Journal of Medicinal Chemistry 2019, 62 (3) , 1420-1442. https://doi.org/10.1021/acs.jmedchem.8b01572
    16. Eric Valeur, Patrick Jimonet. New Modalities, Technologies, and Partnerships in Probe and Lead Generation: Enabling a Mode-of-Action Centric Paradigm. Journal of Medicinal Chemistry 2018, 61 (20) , 9004-9029. https://doi.org/10.1021/acs.jmedchem.8b00378
    17. Christian Steinebach, Stefanie Lindner, Namrata D. Udeshi, Deepak C. Mani, Hannes Kehm, Simon Köpff, Steven A. Carr, Michael Gütschow, Jan Krönke. Homo-PROTACs for the Chemical Knockdown of Cereblon. ACS Chemical Biology 2018, 13 (9) , 2771-2782. https://doi.org/10.1021/acschembio.8b00693
    18. Lucia Wang, Valeria S. Guillen, Naina Sharma, Kevin Flessa, Jian Min, Kathryn E. Carlson, Weiyi Toy, Sara Braqi, Benita S. Katzenellenbogen, John A. Katzenellenbogen, Sarat Chandarlapaty, Abhishek Sharma. New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons. ACS Medicinal Chemistry Letters 2018, 9 (8) , 803-808. https://doi.org/10.1021/acsmedchemlett.8b00106
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    20. Marie Cornu, Thomas Lemaitre, Charline Kieffer, Anne Sophie Voisin-Chiret. PROTAC 2.0: Expanding the frontiers of targeted protein degradation. Drug Discovery Today 2025, 30 (6) , 104376. https://doi.org/10.1016/j.drudis.2025.104376
    21. Huang Su, Yifan Chen, Xuyang Zhao, Zengyi Lu, Tongxuan Wei, Qinguo Liu, Xiyang Liu, Qinhao Zhang, Siqi Bian, Qianwei Qiu, Panzhu Yao, Wenlang Liu, Zheng Zheng, Da Xu, Liqin Zhang. Systematic evolution of functional oligonucleotides for targeted protein degradation. Chem 2025, 11 (5) , 102408. https://doi.org/10.1016/j.chempr.2024.102408
    22. Youmin Zhu, Yu Dai, Yuncai Tian. The Peptide PROTAC Modality: A New Strategy for Drug Discovery. MedComm 2025, 6 (4) https://doi.org/10.1002/mco2.70133
    23. Rouming Peng, Xin Liu, Chun-Chi Chen, Rey-Ting Guo, Jian Min. Development of PROTACs targeting estrogen receptor: an emerging technique for combating endocrine resistance. RSC Medicinal Chemistry 2025, 16 (3) , 1023-1036. https://doi.org/10.1039/D4MD00961D
    24. Katarina Vrbnjak, Raj Nayan Sewduth. Recent Advances in Peptide Drug Discovery: Novel Strategies and Targeted Protein Degradation. Pharmaceutics 2024, 16 (11) , 1486. https://doi.org/10.3390/pharmaceutics16111486
    25. Yawen Dong, Tingting Ma, Ting Xu, Zhangyan Feng, Yonggui Li, Lingling Song, Xiaojun Yao, Charles R. Ashby, Ge-Fei Hao. Characteristic roadmap of linker governs the rational design of PROTACs. Acta Pharmaceutica Sinica B 2024, 14 (10) , 4266-4295. https://doi.org/10.1016/j.apsb.2024.04.007
    26. Zhenjie Wang, Siyao Che, Zhiqiang Yu. PROTAC: Novel degradable approach for different targets to treat breast cancer. European Journal of Pharmaceutical Sciences 2024, 198 , 106793. https://doi.org/10.1016/j.ejps.2024.106793
    27. Suwei Dong, Ji-Shen Zheng, Yiming Li, Huan Wang, Gong Chen, Yongxiang Chen, Gemin Fang, Jun Guo, Chunmao He, Honggang Hu, Xuechen Li, Yanmei Li, Zigang Li, Man Pan, Shan Tang, Changlin Tian, Ping Wang, Bian Wu, Chuanliu Wu, Junfeng Zhao, Lei Liu. Recent advances in chemical protein synthesis: method developments and biological applications. Science China Chemistry 2024, 67 (4) , 1060-1096. https://doi.org/10.1007/s11426-024-1950-1
    28. Xiaoqi Xue, Chen Zhang, Xiaolin Li, Junqiao Wang, Haowei Zhang, Ying Feng, Naihan Xu, Hongyan Li, Chunyan Tan, Yuyang Jiang, Ying Tan. mRNA PROTACs: engineering PROTACs for high‐efficiency targeted protein degradation. MedComm 2024, 5 (2) https://doi.org/10.1002/mco2.478
    29. Huidan Wang, Miao Chen, Xiaoyuan Zhang, Songbo Xie, Jie Qin, Jingrui Li. Peptide-based PROTACs: Current Challenges and Future Perspectives. Current Medicinal Chemistry 2024, 31 (2) , 208-222. https://doi.org/10.2174/0929867330666230130121822
    30. Muzi Ouyang, Ying Feng, Hui Chen, Yanping Liu, Chunyan Tan, Ying Tan. Recent Advances in Optically Controlled PROTAC. Bioengineering 2023, 10 (12) , 1368. https://doi.org/10.3390/bioengineering10121368
    31. Suddhasatwa Banerjee, Sachin Sharma, Amandeep Thakur, Ritika Sachdeva, Ram Sharma, Kunal Nepali, Jing Ping Liou. N-Heterocycle based Degraders (PROTACs) Manifesting Anticancer Efficacy: Recent Advances. Current Drug Targets 2023, 24 (15) , 1184-1208. https://doi.org/10.2174/0113894501273969231102095615
    32. Hannah C. Hymel, Jeffery C. Anderson, Dong Liu, Ted J. Gauthier, Adam T. Melvin. Incorporating a β-hairpin sequence motif to increase intracellular stability of a peptide-based PROTAC. Biochemical Engineering Journal 2023, 199 , 109063. https://doi.org/10.1016/j.bej.2023.109063
    33. Paulina Miziak, Marzena Baran, Ewa Błaszczak, Alicja Przybyszewska-Podstawka, Joanna Kałafut, Jolanta Smok-Kalwat, Magdalena Dmoszyńska-Graniczka, Michał Kiełbus, Andrzej Stepulak. Estrogen Receptor Signaling in Breast Cancer. Cancers 2023, 15 (19) , 4689. https://doi.org/10.3390/cancers15194689
    34. Qiong Li, Li Zhou, Siyuan Qin, Zhao Huang, Bowen Li, Ruolan Liu, Mei Yang, Edouard C. Nice, Huili Zhu, Canhua Huang. Proteolysis-targeting chimeras in biotherapeutics: Current trends and future applications. European Journal of Medicinal Chemistry 2023, 257 , 115447. https://doi.org/10.1016/j.ejmech.2023.115447
    35. Baohua Xie, Bin Xu, Lilan Xin, Yizhou Wei, Xinyi Guo, Chune Dong. Discovery of estrogen receptor α targeting caged hypoxia-responsive PROTACs with an inherent bicyclic skeleton for breast cancer treatment. Bioorganic Chemistry 2023, 137 , 106590. https://doi.org/10.1016/j.bioorg.2023.106590
    36. Matthew N. O’Brien Laramy, Suman Luthra, Matthew F. Brown, Derek W. Bartlett. Delivering on the promise of protein degraders. Nature Reviews Drug Discovery 2023, 22 (5) , 410-427. https://doi.org/10.1038/s41573-023-00652-2
    37. Yu Xue, Andrew A. Bolinger, Jia Zhou. Novel approaches to targeted protein degradation technologies in drug discovery. Expert Opinion on Drug Discovery 2023, 18 (4) , 467-483. https://doi.org/10.1080/17460441.2023.2187777
    38. Hong‐Yi Zhao, Minhang Xin, San‐Qi Zhang. Progress of small molecules for targeted protein degradation: PROTACs and other technologies. Drug Development Research 2023, 84 (2) , 337-394. https://doi.org/10.1002/ddr.22026
    39. Muhammad Zafar Irshad Khan, Adila Nazli, You-Lu Pan, Jian-Zhong Chen. Recent Developments in Medicinal Chemistry and Therapeutic Potential of Anti-Cancer PROTACs-Based Molecules. Current Medicinal Chemistry 2023, 30 (14) , 1576-1622. https://doi.org/10.2174/0929867329666220803112409
    40. Rajni Bala, Rakesh Kumar Sindhu, Reecha Madaan, Shantanu Kumar Yadav. PROTAC: A Novel Drug Delivery Technology for Targeting Proteins in Cancer Cells. Current Drug Discovery Technologies 2023, 20 (2) https://doi.org/10.2174/1570163820666221031124612
    41. Yan Li, Yi Jia, Xiaolin Wang, Hai Shang, Yu Tian. Protein-Targeted Degradation Agents Based on Natural Products. Pharmaceuticals 2023, 16 (1) , 46. https://doi.org/10.3390/ph16010046
    42. Yu Chen, Qingfan Yang, Jinrun Xu, Liyao Tang, Yan Zhang, Fukuan Du, Yueshui Zhao, Xu Wu, Mingxing Li, Jing Shen, Ruilin Ding, Hongying Cao, Wanping Li, Xiaobing Li, Meijuan Chen, Zhigui Wu, Chi Hin Cho, Yu Du, Qinglian Wen, Zhangang Xiao. PROTACs in gastrointestinal cancers. Molecular Therapy - Oncolytics 2022, 27 , 204-223. https://doi.org/10.1016/j.omto.2022.10.012
    43. Xinyi Li, Wenchen Pu, Qingquan Zheng, Min Ai, Song Chen, Yong Peng. Proteolysis-targeting chimeras (PROTACs) in cancer therapy. Molecular Cancer 2022, 21 (1) https://doi.org/10.1186/s12943-021-01434-3
    44. Kun Wang, Xiaoyong Dai, Albert Yu, Chunyan Feng, Kewei Liu, Laiqiang Huang. Peptide-based PROTAC degrader of FOXM1 suppresses cancer and decreases GLUT1 and PD-L1 expression. Journal of Experimental & Clinical Cancer Research 2022, 41 (1) https://doi.org/10.1186/s13046-022-02483-2
    45. Hidetomo Yokoo, Miyako Naganuma, Makoto Oba, Yosuke Demizu. Recent Advances in PROTAC Technology Toward New Therapeutic Modalities. Chemistry & Biodiversity 2022, 19 (11) https://doi.org/10.1002/cbdv.202200828
    46. Wu Ye, Xia Wu, Xiaojia Wang, Xiaoyu Wei, Yuqian Tang, Xianfeng Ouyang, Yuping Gong. The proteolysis targeting chimera GMB-475 combined with dasatinib for the treatment of chronic myeloid leukemia with BCR::ABL1 mutants. Frontiers in Pharmacology 2022, 13 https://doi.org/10.3389/fphar.2022.931772
    47. Angeles C. Tecalco-Cruz, Josué Orlando Ramírez-Jarquín, Marina Macías-Silva, Marcela Sosa-Garrocho, César López-Camarillo. Novel Breast Cancer Treatment by Targeting Estrogen Receptor-Alpha Stability Using Proteolysis-Targeting Chimeras (PROTACs) Technology. 2022, 179-193. https://doi.org/10.36255/exon-publications-breast-cancer-protacs
    48. Sinan Ma, Jianai Ji, Yuanyuan Tong, Yuxuan Zhu, Junwei Dou, Xian Zhang, Shicheng Xu, Tianbao Zhu, Xiaoli Xu, Qidong You, Zhengyu Jiang. Non-small molecule PROTACs (NSM-PROTACs): Protein degradation kaleidoscope. Acta Pharmaceutica Sinica B 2022, 12 (7) , 2990-3005. https://doi.org/10.1016/j.apsb.2022.02.022
    49. Yu Tian, Matthew V. Tirrell, James L. LaBelle. Harnessing the Therapeutic Potential of Biomacromolecules through Intracellular Delivery of Nucleic Acids, Peptides, and Proteins. Advanced Healthcare Materials 2022, 11 (12) https://doi.org/10.1002/adhm.202102600
    50. Angeles C. Tecalco-Cruz, Marina Macías-Silva, Josué Orlando Ramírez-Jarquín, Uri Nimrod Ramírez-Jarquín. Decoding the Therapeutic Implications of the ERα Stability and Subcellular Distribution in Breast Cancer. Frontiers in Endocrinology 2022, 13 https://doi.org/10.3389/fendo.2022.867448
    51. Li Liu, Lihong Shi, Zhaodi Wang, Jun Zeng, Yue Wang, Hongtao Xiao, Yongxia Zhu. Targeting Oncoproteins for Degradation by Small Molecule-Based Proteolysis-Targeting Chimeras (PROTACs) in Sex Hormone-Dependent Cancers. Frontiers in Endocrinology 2022, 13 https://doi.org/10.3389/fendo.2022.839857
    52. Guliang Yang, Haiyan Zhong, Xinxin Xia, Zhiwen Qi, Chengzhang Wang, Shiming Li. Potential application of proteolysis targeting chimera (PROTAC) modification technology in natural products for their targeted protein degradation. Food Science and Human Wellness 2022, 11 (2) , 199-207. https://doi.org/10.1016/j.fshw.2021.11.001
    53. Xiaofang Kang, Hongcheng Zhu. Bone Marrow Mesenchymal Stem Cells (BMSCs) Enhance Endometrial Stromal Cell Migration and Epithelial-Mesenchymal Transition in Adenomyosis Through Upregulation of Neuropilin 1. Journal of Biomaterials and Tissue Engineering 2022, 12 (2) , 352-357. https://doi.org/10.1166/jbt.2022.2845
    54. Rajwinder Kaur, Gaurav Chaudhary, Amritpal Kaur, Pargat Singh, Gagan Deep Longowal, Gayatri P. Sapkale, Sandeep Arora. PROTACs: A Hope for Breast Cancer Patients?. Anti-Cancer Agents in Medicinal Chemistry 2022, 22 (3) , 406-417. https://doi.org/10.2174/1871520621666210308100327
    55. Ota Fuchs. Proteolysis-targeting chimeras (PROTACs) as novel biotechnology for cancer therapy. 2022, 71-88. https://doi.org/10.1016/B978-0-323-90042-3.15001-7
    56. Angeles C. Tecalco-Cruz, Jesús Zepeda-Cervantes, Josué O. Ramírez-Jarquín, Alberto Rojas-Ochoa. Proteolysis-targeting chimeras and their implications in breast cancer. Exploration of Targeted Anti-tumor Therapy 2021, 2 (6) https://doi.org/10.37349/etat.2021.00060
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    65. Zunyuan Wang, Zhen Ma, Zhengrong Shen. Selective degradation of the estrogen receptor in the treatment of cancers. The Journal of Steroid Biochemistry and Molecular Biology 2021, 209 , 105848. https://doi.org/10.1016/j.jsbmb.2021.105848
    66. Ota Fuchs, Radka Bokorova. Preclinical Studies of PROTACs in Hematological Malignancies. Cardiovascular & Hematological Disorders-Drug Targets 2021, 21 (1) , 7-22. https://doi.org/10.2174/1871529X21666210308111546
    67. Guoyi Yan, Xinxin Zhong, Lin Yue, Chunlan Pu, Huifang Shan, Suke Lan, Meng Zhou, Xueyan Hou, Jie Yang, Rui Li. Discovery of a PROTAC targeting ALK with in vivo activity. European Journal of Medicinal Chemistry 2021, 212 , 113150. https://doi.org/10.1016/j.ejmech.2020.113150
    68. Zere Mukhamejanova, Yichen Tong, Qi Xiang, Fang Xu, Jiyan Pang. Recent Advances in the Design and Development of Anticancer Molecules based on PROTAC Technology. Current Medicinal Chemistry 2021, 28 (7) , 1304-1327. https://doi.org/10.2174/0929867327666200312112412
    69. Manibarathi Vaithiyanathan, Hannah C. Hymel, Nora Safa, Olivia M. Sanchez, Jacob H. Pettigrew, Cole S. Kirkpatrick, Ted J. Gauthier, Adam T. Melvin. Kinetic analysis of cellular internalization and expulsion of unstructured D‐chirality cell penetrating peptides. AIChE Journal 2021, 67 (1) https://doi.org/10.1002/aic.17087
    70. Marie T. J. Bluntzer, James O'Connell, Terry S. Baker, Julien Michel, Alison N. Hulme. Designing stapled peptides to inhibit protein‐protein interactions: An analysis of successes in a rapidly changing field. Peptide Science 2021, 113 (1) https://doi.org/10.1002/pep2.24191
    71. Xinrui Yang, He Yin, Richard D. Kim, Jason B. Fleming, Hao Xie. Preclinical and Clinical Advances of Targeted Protein Degradation as a Novel Cancer Therapeutic Strategy: An Oncologist Perspective. Targeted Oncology 2021, 16 (1) , 1-12. https://doi.org/10.1007/s11523-020-00782-2
    72. Shelton R. Boyd, Lyra Chang, Wanderson Rezende, Idris O. Raji, Prasanna Kandel, Secondra L. Holmes, Damian W. Young. Design and Applications of Bifunctional Small Molecules in Biology. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 2021, 1869 (1) , 140534. https://doi.org/10.1016/j.bbapap.2020.140534
    73. Xueyang Jiang, Junting Zhou, Yang Wang, Xin Liu, Kaiying Xu, Jian Xu, Feng Feng, Haopeng Sun. PROTACs suppression of GSK-3β, a crucial kinase in neurodegenerative diseases. European Journal of Medicinal Chemistry 2021, 210 , 112949. https://doi.org/10.1016/j.ejmech.2020.112949
    74. Jing Liu, Jia Ma, Yi Liu, Jun Xia, Yuyun Li, Z. Peter Wang, Wenyi Wei. PROTACs: A novel strategy for cancer therapy. Seminars in Cancer Biology 2020, 67 , 171-179. https://doi.org/10.1016/j.semcancer.2020.02.006
    75. Hongwei Liao, Xiang Li, Lianzheng Zhao, Yalong Wang, Xiaodan Wang, Ye Wu, Xin Zhou, Wei Fu, Lei Liu, Hong-Gang Hu, Ye-Guang Chen. A PROTAC peptide induces durable β-catenin degradation and suppresses Wnt-dependent intestinal cancer. Cell Discovery 2020, 6 (1) https://doi.org/10.1038/s41421-020-0171-1
    76. Xin Li, Yongcheng Song. Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy. Journal of Hematology & Oncology 2020, 13 (1) https://doi.org/10.1186/s13045-020-00885-3
    77. Alberto Ocaña, Atanasio Pandiella. Proteolysis targeting chimeras (PROTACs) in cancer therapy. Journal of Experimental & Clinical Cancer Research 2020, 39 (1) https://doi.org/10.1186/s13046-020-01672-1
    78. Jie Li, Jieqing Liu. PROTAC: A Novel Technology for Drug Development**. ChemistrySelect 2020, 5 (42) , 13232-13247. https://doi.org/10.1002/slct.202003162
    79. Lina Yin, Qingzhong Hu. Chimera induced protein degradation: PROTACs and beyond. European Journal of Medicinal Chemistry 2020, 206 , 112494. https://doi.org/10.1016/j.ejmech.2020.112494
    80. Yuanyuan Shan, Ru Si, Jin Wang, Qingqing Zhang, Jing Li, Yuexiang Ma, Jie Zhang. Discovery of novel anti-angiogenesis agents. Part 11: Development of PROTACs based on active molecules with potency of promoting vascular normalization. European Journal of Medicinal Chemistry 2020, 205 , 112654. https://doi.org/10.1016/j.ejmech.2020.112654
    81. Xin Lin, Hua Xiang, Guoshun Luo. Targeting estrogen receptor α for degradation with PROTACs: A promising approach to overcome endocrine resistance. European Journal of Medicinal Chemistry 2020, 206 , 112689. https://doi.org/10.1016/j.ejmech.2020.112689
    82. Raed Al-Saharin, Sutton Mooney, Hanjo Hellmann. Plant E3 Ligases as Versatile Tools for Novel Drug Development and Plant Bioengineering. 2020, 212-233. https://doi.org/10.1039/9781839160691-00212
    83. Yun‐Kun Qi, Qian Qu, Donald Bierer, Lei Liu. A Diaminodiacid (DADA) Strategy for the Development of Disulfide Surrogate Peptides. Chemistry – An Asian Journal 2020, 15 (18) , 2793-2802. https://doi.org/10.1002/asia.202000609
    84. Divya Bafna, Fuqiang Ban, Paul S. Rennie, Kriti Singh, Artem Cherkasov. Computer-Aided Ligand Discovery for Estrogen Receptor Alpha. International Journal of Molecular Sciences 2020, 21 (12) , 4193. https://doi.org/10.3390/ijms21124193
    85. Shagufta, Irshad Ahmad, Shimy Mathew, Sofia Rahman. Recent progress in selective estrogen receptor downregulators (SERDs) for the treatment of breast cancer. RSC Medicinal Chemistry 2020, 11 (4) , 438-454. https://doi.org/10.1039/C9MD00570F
    86. Qian Qu, Shuai Gao, Fangming Wu, Meng‐Ge Zhang, Ying Li, Long‐Hua Zhang, Donald Bierer, Chang‐Lin Tian, Ji‐Shen Zheng, Lei Liu. Synthesis of Disulfide Surrogate Peptides Incorporating Large‐Span Surrogate Bridges Through a Native‐Chemical‐Ligation‐Assisted Diaminodiacid Strategy. Angewandte Chemie 2020, 132 (15) , 6093-6101. https://doi.org/10.1002/ange.201915358
    87. Qian Qu, Shuai Gao, Fangming Wu, Meng‐Ge Zhang, Ying Li, Long‐Hua Zhang, Donald Bierer, Chang‐Lin Tian, Ji‐Shen Zheng, Lei Liu. Synthesis of Disulfide Surrogate Peptides Incorporating Large‐Span Surrogate Bridges Through a Native‐Chemical‐Ligation‐Assisted Diaminodiacid Strategy. Angewandte Chemie International Edition 2020, 59 (15) , 6037-6045. https://doi.org/10.1002/anie.201915358
    88. Yixiang Jiang, Xuehan Jiang, Xiaodong Shi, Fadeng Yang, Yang Cao, Xuan Qin, Zhanfeng Hou, Mingsheng Xie, Na Liu, Qi Fang, Feng Yin, Wei Han, Zigang Li. α-Helical Motif as Inhibitors of Toxic Amyloid-β Oligomer Generation via Highly Specific Recognition of Amyloid Surface. iScience 2019, 17 , 87-100. https://doi.org/10.1016/j.isci.2019.06.022
    89. Stacey-Lynn Paiva, Craig M Crews. Targeted protein degradation: elements of PROTAC design. Current Opinion in Chemical Biology 2019, 50 , 111-119. https://doi.org/10.1016/j.cbpa.2019.02.022
    90. Yuanyuan Li, Silong Zhang, Jing Zhang, Zhiye Hu, Yuan Xiao, Jian Huang, Chune Dong, Shengtang Huang, Hai-Bing Zhou. Exploring the PROTAC degron candidates: OBHSA with different side chains as novel selective estrogen receptor degraders (SERDs). European Journal of Medicinal Chemistry 2019, 172 , 48-61. https://doi.org/10.1016/j.ejmech.2019.03.058
    91. Dongyuan Wang, Wenjun Li, Rongtong Zhao, Longjian Chen, Na Liu, Yuan Tian, Hui Zhao, Mingsheng Xie, Fei Lu, Qi Fang, Wei Liang, Feng Yin, Zigang Li. Stabilized Peptide HDAC Inhibitors Derived from HDAC1 Substrate H3K56 for the Treatment of Cancer Stem–Like Cells In Vivo. Cancer Research 2019, 79 (8) , 1769-1783. https://doi.org/10.1158/0008-5472.CAN-18-1421
    92. Rajesh Chopra, Amine Sadok, Ian Collins. A critical evaluation of the approaches to targeted protein degradation for drug discovery. Drug Discovery Today: Technologies 2019, 31 , 5-13. https://doi.org/10.1016/j.ddtec.2019.02.002
    93. Gillian F. Watt, Paul Scott-Stevens, Lu Gaohua. Targeted protein degradation in vivo with Proteolysis Targeting Chimeras: Current status and future considerations. Drug Discovery Today: Technologies 2019, 31 , 69-80. https://doi.org/10.1016/j.ddtec.2019.02.005
    94. Jianguo Qi, Gang Zhang. Proteolysis-targeting Chimeras for Targeting Protein for Degradation. Future Medicinal Chemistry 2019, 11 (7) , 723-741. https://doi.org/10.4155/fmc-2018-0557
    95. Angeles C. Tecalco-Cruz, Josué O. Ramírez-Jarquín, Eduardo Cruz-Ramos. Estrogen Receptor Alpha and its Ubiquitination in Breast Cancer Cells. Current Drug Targets 2019, 20 (6) , 690-704. https://doi.org/10.2174/1389450119666181015114041
    96. Yutian Zou, Danhui Ma, Yinyin Wang. The PROTAC technology in drug development. Cell Biochemistry and Function 2019, 37 (1) , 21-30. https://doi.org/10.1002/cbf.3369
    97. Yukihiro Itoh. Chemical Protein Degradation Approach and its Application to Epigenetic Targets. The Chemical Record 2018, 18 (12) , 1681-1700. https://doi.org/10.1002/tcr.201800032
    98. Yingchao Duan, Yuanyuan Guan, Wenping Qin, Xiaoyu Zhai, Bin Yu, Hongmin Liu. Targeting Brd4 for cancer therapy: inhibitors and degraders. MedChemComm 2018, 9 (11) , 1779-1802. https://doi.org/10.1039/C8MD00198G
    99. Weirong Qin, Mingsheng Xie, Xuan Qin, Qi Fang, Feng Yin, Zigang Li. Recent advances in peptidomimetics antagonists targeting estrogen receptor α-coactivator interaction in cancer therapy. Bioorganic & Medicinal Chemistry Letters 2018, 28 (17) , 2827-2836. https://doi.org/10.1016/j.bmcl.2018.05.062
    100. Xuan Qin, Hui Zhao, Yanhong Jiang, Feng Yin, Yuan Tian, Mingsheng Xie, Xiyang Ye, Naihan Xu, Zigang Li. Development of a potent peptide inhibitor of estrogen receptor α. Chinese Chemical Letters 2018, 29 (7) , 1160-1162. https://doi.org/10.1016/j.cclet.2018.04.004
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    Cite this: ACS Chem. Biol. 2018, 13, 3, 628–635
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