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

Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 2: Structure-Based Drug Design and Structure–Activity Relationship

View Author Information
Department of Experimental Oncology, Academic Drug Discovery, European Institute of Oncology, Via Adamello 16, 20139 Milano, Italy
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 1, 27100 Pavia, Italy
§ Crystallography Unit, Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milano, Italy
IFOM- The FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milano, Italy
Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milano, Italy
# Genextra Group, DAC s.r.l., Via Adamello 16, 20139 Milano, Italy
*For P.V.: phone, +39 02 9437 5030; e-mail, [email protected]
*For L.S.: phone, +39 02 9437 5121; e-mail, [email protected]
Cite this: J. Med. Chem. 2017, 60, 5, 1693–1715
Publication Date (Web):February 10, 2017
https://doi.org/10.1021/acs.jmedchem.6b01019
Copyright © 2017 American Chemical Society

    Article Views

    3404

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options
    Supporting Info (5)»

    Abstract

    Abstract Image

    The balance of methylation levels at histone H3 lysine 4 (H3K4) is regulated by KDM1A (LSD1). KDM1A is overexpressed in several tumor types, thus representing an emerging target for the development of novel cancer therapeutics. We have previously described (Part 1, DOI 10.1021.acs.jmedchem.6b01018) the identification of thieno[3,2-b]pyrrole-5-carboxamides as novel reversible inhibitors of KDM1A, whose preliminary exploration resulted in compound 2 with biochemical IC50 = 160 nM. We now report the structure-guided optimization of this chemical series based on multiple ligand/KDM1A-CoRest cocrystal structures, which led to several extremely potent inhibitors. In particular, compounds 46, 49, and 50 showed single-digit nanomolar IC50 values for in vitro inhibition of KDM1A, with high selectivity in secondary assays. In THP-1 cells, these compounds transcriptionally affected the expression of genes regulated by KDM1A such as CD14, CD11b, and CD86. Moreover, 49 and 50 showed a remarkable anticlonogenic cell growth effect on MLL-AF9 human leukemia cells.

    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/acs.jmedchem.6b01019.

    • Synthetic procedures for the preparation of compounds 20e, 21e, 23e28e, and 44; material and methods for biochemical and cellular assays; data collection and refinement statistics for compounds 15, 17, 34, 49, and 50; HOMO values and localization; HOMO pictures for compounds 15, 2026, and 44; calculated physicochemical properties (molecular surface area, AlogP, and Log D) (PDF)

    • Molecular formula strings (CSV)

    • Protein Target (PDB)

    • Compound 2, pose A (PDB)

    • Compound 2, pose B (PDB)

    Accession Codes

    Atomic coordinates for the crystal structures of KDM1A with compounds 15, 17, 34, 49, and 50 can be accessed using PDB codes 5LGT, 5LHG, 5LGU, 5LHH, and 5LHI, respectively. Authors will release the atomic coordinates and experimental data upon article publication.

    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 58 publications.

    1. Kecheng Yang, Hongmin Liu. Uncovering New Conformational States of the Substrate Binding Pocket of LSD1 Potential for Inhibitor Design via Funnel Metadynamics. The Journal of Physical Chemistry B 2024, 128 (1) , 137-149. https://doi.org/10.1021/acs.jpcb.3c06900
    2. Yihui Song, Shu Wang, Bin Yu. Structural and Functional Landscape of FAD-Dependent Histone Lysine Demethylases for New Drug Discovery. Journal of Medicinal Chemistry 2023, 66 (1) , 71-94. https://doi.org/10.1021/acs.jmedchem.2c01324
    3. Xing-Jie Dai, Ying Liu, Lei-Peng Xue, Xiao-Peng Xiong, Ying Zhou, Yi-Chao Zheng, Hong-Min Liu. Reversible Lysine Specific Demethylase 1 (LSD1) Inhibitors: A Promising Wrench to Impair LSD1. Journal of Medicinal Chemistry 2021, 64 (5) , 2466-2488. https://doi.org/10.1021/acs.jmedchem.0c02176
    4. Matthew D. Lloyd. High-Throughput Screening for the Discovery of Enzyme Inhibitors. Journal of Medicinal Chemistry 2020, 63 (19) , 10742-10772. https://doi.org/10.1021/acs.jmedchem.0c00523
    5. Alessia Romussi, Anna Cappa, Paola Vianello, Silvia Brambillasca, Maria Rosaria Cera, Roberto Dal Zuffo, Giovanni Fagà, Raimondo Fattori, Loris Moretti, Paolo Trifirò, Manuela Villa, Stefania Vultaggio, Valentina Cecatiello, Sebastiano Pasqualato, Giulio Dondio, Chi Wai Eric So, Saverio Minucci, Luca Sartori, Mario Varasi, Ciro Mercurio. Discovery of Reversible Inhibitors of KDM1A Efficacious in Acute Myeloid Leukemia Models. ACS Medicinal Chemistry Letters 2020, 11 (5) , 754-759. https://doi.org/10.1021/acsmedchemlett.9b00604
    6. Daniel P. Mould, Cristina Alli, Ulf Bremberg, Sharon Cartic, Allan M. Jordan, Matthis Geitmann, Alba Maiques-Diaz, Alison E. McGonagle, Tim C. P. Somervaille, Gary J. Spencer, Fabrice Turlais, and Donald Ogilvie . Development of (4-Cyanophenyl)glycine Derivatives as Reversible Inhibitors of Lysine Specific Demethylase 1. Journal of Medicinal Chemistry 2017, 60 (19) , 7984-7999. https://doi.org/10.1021/acs.jmedchem.7b00462
    7. Luca Sartori, Ciro Mercurio, Federica Amigoni, Anna Cappa, Giovanni Fagá, Raimondo Fattori, Elena Legnaghi, Giuseppe Ciossani, Andrea Mattevi, Giuseppe Meroni, Loris Moretti, Valentina Cecatiello, Sebastiano Pasqualato, Alessia Romussi, Florian Thaler, Paolo Trifiró, Manuela Villa, Stefania Vultaggio, Oronza A. Botrugno, Paola Dessanti, Saverio Minucci, Elisa Zagarrí, Daniele Carettoni, Lucia Iuzzolino, Mario Varasi, and Paola Vianello . Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 1: High-Throughput Screening and Preliminary Exploration. Journal of Medicinal Chemistry 2017, 60 (5) , 1673-1692. https://doi.org/10.1021/acs.jmedchem.6b01018
    8. Li Long, Han Zhang, ZhiHui Zhou, Lei Duan, Dang Fan, Ran Wang, Shan Xu, Dan Qiao, Wufu Zhu. Pyrrole-containing hybrids as potential anticancer agents: An insight into current developments and structure-activity relationships. European Journal of Medicinal Chemistry 2024, 273 , 116470. https://doi.org/10.1016/j.ejmech.2024.116470
    9. Shukai Gu, Lingjie Bao, Yuwei Yang, Yihao Zhao, Henry Hoi Yee Tong, Liwei Liu, Huanxiang Liu, Tingjun Hou, Yu Kang. AMGC is a multiple-task graph neutral network for epigenetic target profiling. Cell Reports Physical Science 2024, 5 (3) , 101850. https://doi.org/10.1016/j.xcrp.2024.101850
    10. Deping Li, Hailiu Liang, Yifei Wei, Hao Xiao, Xiaopeng Peng, Wanyi Pan. Exploring the potential of histone demethylase inhibition in multi-therapeutic approaches for cancer treatment. European Journal of Medicinal Chemistry 2024, 264 , 115999. https://doi.org/10.1016/j.ejmech.2023.115999
    11. Di Han, Jiarui Lu, Baoyi Fan, Wenfeng Lu, Yiwei Xue, Meiting Wang, Taigang Liu, Shaoli Cui, Qinghe Gao, Yingchao Duan, Yongtao Xu. Lysine-Specific Demethylase 1 Inhibitors: A Comprehensive Review Utilizing Computer-Aided Drug Design Technologies. Molecules 2024, 29 (2) , 550. https://doi.org/10.3390/molecules29020550
    12. Konrad Diedrich, Bennet Krause, Ole Berg, Matthias Rarey. PoseEdit: enhanced ligand binding mode communication by interactive 2D diagrams. Journal of Computer-Aided Molecular Design 2023, 37 (10) , 491-503. https://doi.org/10.1007/s10822-023-00522-4
    13. Zhili Yin, Shaohui Liu, Xiaoyue Yang, Mengguo Chen, Jiangfeng Du, Hongmin Liu, Longhua Yang. LSD1-Based Reversible Inhibitors Virtual Screening and Binding Mechanism Computational Study. Molecules 2023, 28 (14) , 5315. https://doi.org/10.3390/molecules28145315
    14. Jiyong Wu, Jing Nie, Yepeng Luan, Yanjiao Ding. Hybrid Histone Deacetylase Inhibitor: An Effective Strategy for Cancer Therapy. Current Medicinal Chemistry 2023, 30 (20) , 2267-2311. https://doi.org/10.2174/0929867329666220826163626
    15. Du’a Al bustanji, Soraya Alnabulsi, Enas A. Al-Hurani. Hit-to-lead optimization of amino-carboxamide benzothiazoles as LSD1 inhibitors. Medicinal Chemistry Research 2023, 32 (5) , 910-929. https://doi.org/10.1007/s00044-023-03046-6
    16. Beatrice Noce, Elisabetta Di Bello, Rossella Fioravanti, Antonello Mai. LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials. Frontiers in Pharmacology 2023, 14 https://doi.org/10.3389/fphar.2023.1120911
    17. Dong Wang, Zhenxing Wu, Chao Shen, Lingjie Bao, Hao Luo, Zhe Wang, Hucheng Yao, De-Xin Kong, Cheng Luo, Tingjun Hou. Learning with uncertainty to accelerate the discovery of histone lysine-specific demethylase 1A (KDM1A/LSD1) inhibitors. Briefings in Bioinformatics 2023, 24 (1) https://doi.org/10.1093/bib/bbac592
    18. Shada J. Alabed, Malek Zihlif, Mutasem Taha. Discovery of new potent lysine specific histone demythelase-1 inhibitors (LSD-1) using structure based and ligand based molecular modelling and machine learning. RSC Advances 2022, 12 (55) , 35873-35895. https://doi.org/10.1039/D2RA05102H
    19. Xiangyu Zhang, Yixiang Sun, Hailan Huang, Xinran Wang, Tianxiao Wu, Wenbo Yin, Xiaojia Li, Lin Wang, Yanting Gu, Dongmei Zhao, Maosheng Cheng. Identification of novel indole derivatives as highly potent and efficacious LSD1 inhibitors. European Journal of Medicinal Chemistry 2022, 239 , 114523. https://doi.org/10.1016/j.ejmech.2022.114523
    20. Rahul D. Jawarkar, Ravindra L. Bakal, Nobendu Mukherjee, Arabinda Ghosh, Magdi E. A. Zaki, Sami A. AL-Hussain, Aamal A. Al-Mutairi, Abdul Samad, Ajaykumar Gandhi, Vijay H. Masand. QSAR Evaluations to Unravel the Structural Features in Lysine-Specific Histone Demethylase 1A Inhibitors for Novel Anticancer Lead Development Supported by Molecular Docking, MD Simulation and MMGBSA. Molecules 2022, 27 (15) , 4758. https://doi.org/10.3390/molecules27154758
    21. Ye Jin, Tianjia Liu, Haoming Luo, Yangyang Liu, Da Liu. Targeting Epigenetic Regulatory Enzymes for Cancer Therapeutics: Novel Small-Molecule Epidrug Development. Frontiers in Oncology 2022, 12 https://doi.org/10.3389/fonc.2022.848221
    22. Yixiang Sun, Ruicheng Lv, Tianxiao Wu, Xiangyu Zhang, Yin Sun, Jiangkun Yan, Ziheng Zhang, Dongmei Zhao, Maosheng Cheng. Design, synthesis, and biological evaluation of coumarin analogs as novel LSD1 inhibitors. Archiv der Pharmazie 2022, 355 (2) https://doi.org/10.1002/ardp.202100311
    23. Xiangyu Zhang, Xinran Wang, Tianxiao Wu, Wenbo Yin, Jiangkun Yan, Yixiang Sun, Dongmei Zhao. Therapeutic potential of targeting LSD1/ KDM1A in cancers. Pharmacological Research 2022, 175 , 105958. https://doi.org/10.1016/j.phrs.2021.105958
    24. Xiangyu Zhang, Yixiang Sun, Ziheng Zhang, Hanxun Wang, Jian Wang, Dongmei Zhao. Intermolecular insights into allosteric inhibition of histone lysine-specific demethylase 1. Biochimica et Biophysica Acta (BBA) - General Subjects 2021, 1865 (11) , 129990. https://doi.org/10.1016/j.bbagen.2021.129990
    25. Avineesh Singh, Vijay K. Patel, Harish Rajak. Appraisal of pyrrole as connecting unit in hydroxamic acid based histone deacetylase inhibitors: Synthesis, anticancer evaluation and molecular docking studies. Journal of Molecular Structure 2021, 1240 , 130590. https://doi.org/10.1016/j.molstruc.2021.130590
    26. Jiangkun Yan, Yanting Gu, Yixiang Sun, Ziheng Zhang, Xiangyu Zhang, Xinran Wang, Tianxiao Wu, Dongmei Zhao, Maosheng Cheng. Design, synthesis, and biological evaluation of 5‐aminotetrahydroquinoline‐based LSD1 inhibitors acting on Asp375. Archiv der Pharmazie 2021, 354 (8) https://doi.org/10.1002/ardp.202100102
    27. Bo Fang, Chunsheng Hu, Yong Ding, Hongxia Qin, Yafei Luo, Zhigang Xu, Jiangping Meng, Zhongzhu Chen. Discovery of 4 H ‐thieno[3,2‐ b ]pyrrole derivatives as potential anticancer agents. Journal of Heterocyclic Chemistry 2021, 58 (8) , 1610-1627. https://doi.org/10.1002/jhet.4285
    28. Ying-Chao Duan, Lin-Feng Jin, Hong-Mei Ren, Shao-Jie Zhang, Yue-Jiao Liu, Yong-Tao Xu, Zi-Hao He, Yu Song, Hang Yuan, Shu-Hui Chen, Yuan-Yuan Guan. Design, synthesis, and biological evaluation of novel dual inhibitors targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDAC) for treatment of gastric cancer. European Journal of Medicinal Chemistry 2021, 220 , 113453. https://doi.org/10.1016/j.ejmech.2021.113453
    29. Xiangyu Zhang, Hailan Huang, Ziheng Zhang, Jiangkun Yan, Tianxiao Wu, Wenbo Yin, Yixiang Sun, Xinran Wang, Yanting Gu, Dongmei Zhao, Maosheng Cheng. Design, synthesis and biological evaluation of novel benzofuran derivatives as potent LSD1 inhibitors. European Journal of Medicinal Chemistry 2021, 220 , 113501. https://doi.org/10.1016/j.ejmech.2021.113501
    30. Andrea Angeli, Victor Kartsev, Anthi Petrou, Mariana Pinteala, Roman M. Vydzhak, Svitlana Y. Panchishin, Volodymyr Brovarets, Viviana De Luca, Clemente Capasso, Athina Geronikaki, Claudiu T. Supuran. New Sulfanilamide Derivatives Incorporating Heterocyclic Carboxamide Moieties as Carbonic Anhydrase Inhibitors. Pharmaceuticals 2021, 14 (8) , 828. https://doi.org/10.3390/ph14080828
    31. Zhong Shao, Fang Wang, Jingqi Shi, Lifang Ma, Ziyuan Li. Synergetic copper/TEMPO-catalysed benzylic C–H imidation with N -fluorobenzenesulfonimide at room temperature and tandem conversions with alcohols or arenes. Organic Chemistry Frontiers 2021, 8 (13) , 3298-3307. https://doi.org/10.1039/D1QO00340B
    32. Elena Yu. Schmidt, Nadezhda V. Semenova, Inna V. Tatarinova, Igor A. Ushakov, Alexander V. Vashchenko, Boris A. Trofimov. Functionalized Thieno[3,2‐ b ]pyrroles from Acylthiophenes, Acetylene Gas and Hydrazines in Two Steps. European Journal of Organic Chemistry 2021, 2021 (19) , 2802-2806. https://doi.org/10.1002/ejoc.202100377
    33. Xiangyu Zhang, Jiangkun Yan, Hanxun Wang, Ying Wang, Jian Wang, Dongmei Zhao. Molecular docking, 3D-QSAR, and molecular dynamics simulations of thieno[3,2-b]pyrrole derivatives against anticancer targets of KDM1A/LSD1. Journal of Biomolecular Structure and Dynamics 2021, 39 (4) , 1189-1202. https://doi.org/10.1080/07391102.2020.1726819
    34. Dong-Jun Fu, Jun Li, Bin Yu. Annual review of LSD1/KDM1A inhibitors in 2020. European Journal of Medicinal Chemistry 2021, 214 , 113254. https://doi.org/10.1016/j.ejmech.2021.113254
    35. S. A. Torosyan, Z. F. Nuriakhmetova, F. A. Gimalova, M. S. Miftakhov. New Carboxamides of the Thieno[3,2-b]pyrrole Series. Russian Journal of Organic Chemistry 2020, 56 (10) , 1850-1853. https://doi.org/10.1134/S1070428020100309
    36. Samir Mehndiratta, Jing-Ping Liou. Histone lysine specific demethylase 1 inhibitors. RSC Medicinal Chemistry 2020, 11 (9) , 969-981. https://doi.org/10.1039/D0MD00141D
    37. Xinran Wang, Cai Zhang, Xiangyu Zhang, Jiangkun Yan, Jiming Wang, Qinwen Jiang, Liyu Zhao, Dongmei Zhao, Maosheng Cheng. Design, synthesis and biological evaluation of tetrahydroquinoline-based reversible LSD1 inhibitors. European Journal of Medicinal Chemistry 2020, 194 , 112243. https://doi.org/10.1016/j.ejmech.2020.112243
    38. Yongtao Xu, Zihao He, Hongyi Liu, Yifan Chen, Yunlong Gao, Songjie Zhang, Meiting Wang, Xiaoyuan Lu, Chang Wang, Zongya Zhao, Yan Liu, Junqiang Zhao, Yi Yu, Min Yang. 3D-QSAR, molecular docking, and molecular dynamics simulation study of thieno[3,2- b ]pyrrole-5-carboxamide derivatives as LSD1 inhibitors. RSC Advances 2020, 10 (12) , 6927-6943. https://doi.org/10.1039/C9RA10085G
    39. Soraya Alnabulsi, Enas A. Al-Hurani, Nizar A. Al-shar'i, Tamam El-Elimat. Amino-carboxamide benzothiazoles as potential LSD1 hit inhibitors. Part I: Computational fragment-based drug design. Journal of Molecular Graphics and Modelling 2019, 93 , 107440. https://doi.org/10.1016/j.jmgm.2019.107440
    40. S. A. Torosyan, Z. F. Nuriakhmetova, F. A. Gimalova, M. S. Miftakhov. 4H-Thieno[3,2-b]pyrrole-5-carboxylate Conjugates with Taurine and Its Tetrabutylammonium Salt. Russian Journal of Organic Chemistry 2019, 55 (12) , 1902-1906. https://doi.org/10.1134/S1070428019120157
    41. Yuan Fang, Guochao Liao, Bin Yu. LSD1/KDM1A inhibitors in clinical trials: advances and prospects. Journal of Hematology & Oncology 2019, 12 (1) https://doi.org/10.1186/s13045-019-0811-9
    42. Yongtao Xu, Zihao He, Min Yang, Yunlong Gao, Linfeng Jin, Meiting Wang, Yichao Zheng, Xiaoyuan Lu, Songjie Zhang, Chang Wang, Zongya Zhao, Junqiang Zhao, Qinghe Gao, Yingchao Duan. Investigating the Binding Mode of Reversible LSD1 Inhibitors Derived from Stilbene Derivatives by 3D-QSAR, Molecular Docking, and Molecular Dynamics Simulation. Molecules 2019, 24 (24) , 4479. https://doi.org/10.3390/molecules24244479
    43. Xu-Dong Sun, Yi-Chao Zheng, Chao-Ya Ma, Jing Yang, Qi-Bing Gao, Ying Yan, Zhi-Zheng Wang, Wen Li, Wen Zhao, Hong-Min Liu, Lina Ding. Identifying the novel inhibitors of lysine-specific demethylase 1 (LSD1) combining pharmacophore-based and structure-based virtual screening. Journal of Biomolecular Structure and Dynamics 2019, 37 (16) , 4200-4214. https://doi.org/10.1080/07391102.2018.1538903
    44. Shuai Wang, Zhong-Rui Li, Feng-Zhi Suo, Xiao-Han Yuan, Bin Yu, Hong-Min Liu. Synthesis, structure-activity relationship studies and biological characterization of new [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1/KDM1A inhibitors. European Journal of Medicinal Chemistry 2019, 167 , 388-401. https://doi.org/10.1016/j.ejmech.2019.02.039
    45. Adam Lee, M. Teresa Borrello, A. Ganesan. LSD (Lysine‐Specific Demethylase): A Decade‐Long Trip from Discovery to Clinical Trials. 2019, 221-261. https://doi.org/10.1002/9783527809257.ch10
    46. Chiara Luise, Tino Heimburg, Berin Karaman, Dina Robaa, Wolfgang Sippl. Computer‐based Lead Identification for Epigenetic Targets. 2019, 45-77. https://doi.org/10.1002/9783527809257.ch3
    47. Takayoshi Suzuki. Lysine-Specific Histone Demethylases 1/2 (LSD1/2) and Their Inhibitors. 2019, 197-219. https://doi.org/10.1007/7355_2019_74
    48. Dina Robaa, Jelena Melesina, Chiara Luise, Wolfgang Sippl. Structure-Based Design of Epigenetic Inhibitors. 2019, 455-486. https://doi.org/10.1007/7355_2019_80
    49. Bin Yu, Hong-Min Liu. Pharmacoepigenetics of LSD1 Inhibitors in Cancer. 2019, 523-530. https://doi.org/10.1016/B978-0-12-813939-4.00014-0
    50. Xudong Sun, Lina Ding, Hong-Min Liu. Probing the binding mode and unbinding mechanism of LSD1 inhibitors by combined computational methods. Physical Chemistry Chemical Physics 2018, 20 (47) , 29833-29846. https://doi.org/10.1039/C8CP03090A
    51. Siyuan Xu, Chen Zhou, Rongfeng Liu, Qihua Zhu, Yungen Xu, Fei Lan, Xiaoming Zha. Optimization of 5-arylidene barbiturates as potent, selective, reversible LSD1 inhibitors for the treatment of acute promyelocytic leukemia. Bioorganic & Medicinal Chemistry 2018, 26 (17) , 4871-4880. https://doi.org/10.1016/j.bmc.2018.08.026
    52. Seda A. Torosyan, Zoya F. Nuriakhmetova, Vadim V. Zagitov, Fanusa A. Gimalova, Mansur S. Miftakhov. New 4H-thieno[3,2-b]pyrrole-5-carboxamides. Chemistry of Heterocyclic Compounds 2018, 54 (8) , 819-822. https://doi.org/10.1007/s10593-018-2355-2
    53. Jiayue Xi, Siyuan Xu, Lulu Zhang, Xueyuan Bi, Yanshen Ren, Yu-Chih Liu, Yueqing Gu, Yungen Xu, Fei Lan, Xiaoming Zha. Design, synthesis and biological activity of 4-(4-benzyloxy)phenoxypiperidines as selective and reversible LSD1 inhibitors. Bioorganic Chemistry 2018, 78 , 7-16. https://doi.org/10.1016/j.bioorg.2018.02.016
    54. Hideaki Niwa, Shin Sato, Tomoko Hashimoto, Kenji Matsuno, Takashi Umehara. Crystal Structure of LSD1 in Complex with 4-[5-(Piperidin-4-ylmethoxy)-2-(p-tolyl)pyridin-3-yl]benzonitrile. Molecules 2018, 23 (7) , 1538. https://doi.org/10.3390/molecules23071538
    55. A. Ganesan. Epigenetic drug discovery: a success story for cofactor interference. Philosophical Transactions of the Royal Society B: Biological Sciences 2018, 373 (1748) , 20170069. https://doi.org/10.1098/rstb.2017.0069
    56. Priya Chacko, Kalegowda Shivashankar. I 2 -catalyzed one-pot synthesis of benzofuro/thieno[2,3- b ]pyrrole motifs. Tetrahedron 2018, 74 (13) , 1520-1526. https://doi.org/10.1016/j.tet.2018.02.013
    57. Daniel P. Mould, Ulf Bremberg, Allan M. Jordan, Matthis Geitmann, Alison E. McGonagle, Tim C.P. Somervaille, Gary J. Spencer, Donald J. Ogilvie. Development and evaluation of 4-(pyrrolidin-3-yl)benzonitrile derivatives as inhibitors of lysine specific demethylase 1. Bioorganic & Medicinal Chemistry Letters 2017, 27 (20) , 4755-4759. https://doi.org/10.1016/j.bmcl.2017.08.052
    58. Xiaoli Fu, Peng Zhang, Bin Yu. Advances toward LSD1 inhibitors for cancer therapy. Future Medicinal Chemistry 2017, 9 (11) , 1227-1242. https://doi.org/10.4155/fmc-2017-0068

    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