ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Development of Stabilized Peptide-Based PROTACs against Estrogen Receptor α

  • Yanhong Jiang
    Yanhong Jiang
    Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
  • 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
  • Longjian Chen
    Longjian Chen
    Key Lab of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China
  • 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]
  • , and 
  • 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
Cite this: ACS Chem. Biol. 2018, 13, 3, 628–635
Publication Date (Web):December 22, 2017
https://doi.org/10.1021/acschembio.7b00985
Copyright © 2017 American Chemical Society

    Article Views

    7534

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options
    Supporting Info (1)»

    Abstract

    Abstract Image

    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.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    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)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 86 publications.

    1. 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
    2. 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
    3. 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
    4. 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
    5. 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
    6. Xuan Qin, Hailing Chen, Licheng Tu, Yue Ma, Na Liu, Haowei Zhang, Di Li, Bernd Riedl, Donald Bierer, Feng Yin, Zigang Li. Potent Inhibition of HIF1α and p300 Interaction by a Constrained Peptide Derived from CITED2. Journal of Medicinal Chemistry 2021, 64 (18) , 13693-13703. https://doi.org/10.1021/acs.jmedchem.1c01043
    7. 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
    8. 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
    9. 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
    10. 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
    11. 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
    12. 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
    13. 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
    14. 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
    15. 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
    16. 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
    17. 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
    18. 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
    19. 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
    20. 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
    21. 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
    22. 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
    23. 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
    24. 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
    25. 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
    26. 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
    27. 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
    28. 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
    29. 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
    30. 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
    31. 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
    32. 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
    33. 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
    34. 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
    35. 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
    36. 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
    37. 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
    38. 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
    39. 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
    40. 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
    41. 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
    42. 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
    43. Gilad Goldhirsh, Yelena Kravtsova-Ivantsiv, Gandhesiri Satish, Tamar Ziv, Ashraf Brik, Aaron Ciechanover. A short binding site in the KPC1 ubiquitin ligase mediates processing of NF-κB1 p105 to p50: A potential for a tumor-suppressive PROTAC. Proceedings of the National Academy of Sciences 2021, 118 (49) https://doi.org/10.1073/pnas.2117254118
    44. Li Duan, Xiao Xu, Limei Xu, Caining Wen, Kan Ouyang, Zigang Li, Yujie Liang. ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis. Frontiers in Pharmacology 2021, 12 https://doi.org/10.3389/fphar.2021.764154
    45. Olga D. Jarosińska, Stefan G. D. Rüdiger. Molecular Strategies to Target Protein Aggregation in Huntington’s Disease. Frontiers in Molecular Biosciences 2021, 8 https://doi.org/10.3389/fmolb.2021.769184
    46. Gregory R. Hughes, Ashley P. Dudey, Andrew M. Hemmings, Andrew Chantry. Frontiers in PROTACs. Drug Discovery Today 2021, 26 (10) , 2377-2383. https://doi.org/10.1016/j.drudis.2021.04.010
    47. Hidetomo Yokoo, Nobumichi Ohoka, Mami Takyo, Takahito Ito, Keisuke Tsuchiya, Takashi Kurohara, Kiyoshi Fukuhara, Takao Inoue, Mikihiko Naito, Yosuke Demizu. Peptide Stapling Improves the Sustainability of a Peptide-Based Chimeric Molecule That Induces Targeted Protein Degradation. International Journal of Molecular Sciences 2021, 22 (16) , 8772. https://doi.org/10.3390/ijms22168772
    48. Louise M. Sternicki, Jim Nonomiya, Miaomiao Liu, Melinda M. Mulvihill, Ronald J. Quinn. Native Mass Spectrometry for the Study of PROTAC GNE‐987‐Containing Ternary Complexes. ChemMedChem 2021, 16 (14) , 2206-2210. https://doi.org/10.1002/cmdc.202100113
    49. Jing Liu, Yunhua Peng, Wenyi Wei. Light-Controllable PROTACs for Temporospatial Control of Protein Degradation. Frontiers in Cell and Developmental Biology 2021, 9 https://doi.org/10.3389/fcell.2021.678077
    50. Matylda Anna Izert, Maria Magdalena Klimecka, Maria Wiktoria Górna. Applications of Bacterial Degrons and Degraders — Toward Targeted Protein Degradation in Bacteria. Frontiers in Molecular Biosciences 2021, 8 https://doi.org/10.3389/fmolb.2021.669762
    51. 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
    52. 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
    53. 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
    54. 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
    55. 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
    56. 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
    57. 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
    58. 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
    59. 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
    60. 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
    61. 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
    62. 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
    63. Jie Li, Jieqing Liu. PROTAC: A Novel Technology for Drug Development**. ChemistrySelect 2020, 5 (42) , 13232-13247. https://doi.org/10.1002/slct.202003162
    64. 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
    65. 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
    66. 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
    67. 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
    68. 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
    69. 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
    70. 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
    71. 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
    72. 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
    73. 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
    74. 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
    75. 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
    76. 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
    77. 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
    78. 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
    79. 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
    80. 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
    81. 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
    82. 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
    83. 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
    84. 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
    85. 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
    86. Fang Yuan, Yuan Tian, Weirong Qin, Jingxu Li, Dan Yang, Bingchuan Zhao, Feng Yin, Zigang Li. Evaluation of topologically distinct constrained antimicrobial peptides with broad-spectrum antimicrobial activity. Organic & Biomolecular Chemistry 2018, 16 (32) , 5764-5770. https://doi.org/10.1039/C8OB00483H

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect