ACS Publications. Most Trusted. Most Cited. Most Read
Small Molecules Selectively Targeting Sigma-1 Receptor for the Treatment of Neurological Diseases

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Med. Chem. 2020, 63, 24, 15187-15217
    Perspective

    Small Molecules Selectively Targeting Sigma-1 Receptor for the Treatment of Neurological Diseases
    Click to copy article linkArticle link copied!

    • Na Ye*
      Na Ye
      Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China
      *Phone: +86 (512) 65881161; fax, +86 (512) 65880369; email, [email protected]
      More by Na Ye
      View Biography
      Orcidhttp://orcid.org/0000-0003-3612-1771
    • Wangzhi Qin
      Wangzhi Qin
      Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China
      More by Wangzhi Qin
      View Biography
    • Sheng Tian
      Sheng Tian
      Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China
      More by Sheng Tian
      View Biography
    • Qingfeng Xu
      Qingfeng Xu
      Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China
      More by Qingfeng Xu
      View Biography
    • Eric A. Wold
      Eric A. Wold
      Chemical Biology Program, Department of Pharmacology and Toxicology, and Center for Addiction Research, University of Texas Medical Branch, Galveston, Texas 77555, United States
      More by Eric A. Wold
      View Biography
      Orcidhttp://orcid.org/0000-0001-6434-7562
    • Jia Zhou*
      Jia Zhou
      Chemical Biology Program, Department of Pharmacology and Toxicology, and Center for Addiction Research, University of Texas Medical Branch, Galveston, Texas 77555, United States
      *Phone:+1 (409) 772-9748; fax, +1 (409) 772-9648; email, [email protected]
      More by Jia Zhou
      View Biography
      Orcidhttp://orcid.org/0000-0002-2811-1090
    • Xue-Chu Zhen*
      Xue-Chu Zhen
      Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China
      *Phone: + 86 (512) 65880369; fax, +86 (512) 65880369; email, [email protected]
      More by Xue-Chu Zhen
      View Biography
    Other Access Options

    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2020, 63, 24, 15187–15217
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jmedchem.0c01192
    Published October 28, 2020
    Copyright © 2020 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    The sigma-1 (σ1) receptor, an enigmatic protein originally classified as an opioid receptor subtype, is now understood to possess unique structural and functional features of its own and play critical roles to widely impact signaling transduction by interacting with receptors, ion channels, lipids, and kinases. The σ1 receptor is implicated in modulating learning, memory, emotion, sensory systems, neuronal development, and cognition and accordingly is now an actively pursued drug target for various neurological and neuropsychiatric disorders. Evaluation of the five selective σ1 receptor drug candidates (pridopidine, ANAVEX2-73, SA4503, S1RA, and T-817MA) that have entered clinical trials has shown that reaching clinical approval remains an evasive and important goal. This review provides up-to-date information on the selective targeting of σ1 receptors, including their history, function, reported crystal structures, and roles in neurological diseases, as well as a useful collation of new chemical entities as σ1 selective orthosteric ligands or allosteric modulators.

    Copyright © 2020 American Chemical Society

    Subjects

    what are subjects

    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. Add or change your institution or let them know you’d like them to include access.

    Cited By

    Click to copy section linkSection link copied!
    Citation Statements
    Explore this article's citation statements on scite.ai
    powered by  Scite

    This article is cited by 61 publications.

    1. Tao Wang, Na Sun, Yanxi Ma, Song Zhang. Recent Advances in the Development of Sigma Receptor (Radio)Ligands and Their Application in Tumors. ACS Pharmacology & Translational Science 2025, 8 (4) , 951-977. https://doi.org/10.1021/acsptsci.4c00711
    2. Zhuang Miao, Yuhan Zhong, Yu Gan, Kequan Fu, Wencheng Liu, Zhihua Cao, Tiantian Zhao, Ziyuan Li, Ao Hai, Yanlai Peng, Zeping Zuo, Tian Zhang, Shilong Hu, Chunxia Chen, Ting Kang, Tianguang Huang, Dong Guo, Bowen Ke. A Novel Bifunctional μOR Agonist and σ1R Antagonist with Potent Analgesic Responses and Reduced Adverse Effects. Journal of Medicinal Chemistry 2023, 66 (23) , 16257-16275. https://doi.org/10.1021/acs.jmedchem.3c01637
    3. Liefeng Hu, Shuting Li, Yonggang Lv. pH-Sensitive Cationic Polymer/DNA Nano-assemblies for Efficient Gene Transfection in Neuroma Cells. ACS Applied Nano Materials 2023, 6 (12) , 10559-10568. https://doi.org/10.1021/acsanm.3c01520
    4. Run-Duo Gao, Michelle Taylor, Tamara McInnis, Zhenglan Chen, Sadakatali S. Gori, Heather M. LaPorte, Maxime A. Siegler, Janet L. Neisewander, Robert H. Mach, Meharvan Singh, Barbara S. Slusher, Rana Rais, Robert R. Luedtke, Takashi Tsukamoto. Synthesis and Pharmacological Characterization of a Difluorinated Analogue of Reduced Haloperidol as a Sigma-1 Receptor Ligand. ACS Chemical Neuroscience 2023, 14 (5) , 947-957. https://doi.org/10.1021/acschemneuro.2c00791
    5. Bengisu Turgutalp, Prabesh Bhattarai, Tugba Ercetin, Chiara Luise, Rengin Reis, Enise Ece Gurdal, Andreas Isaak, Derya Biriken, Elisabeth Dinter, Hande Sipahi, Dirk Schepmann, Anna Junker, Bernhard Wünsch, Wolfgang Sippl, Hayrettin Ozan Gulcan, Caghan Kizil, Mine Yarim. Discovery of Potent Cholinesterase Inhibition-Based Multi-Target-Directed Lead Compounds for Synaptoprotection in Alzheimer’s Disease. Journal of Medicinal Chemistry 2022, 65 (18) , 12292-12318. https://doi.org/10.1021/acs.jmedchem.2c01003
    6. Samuel Obeng, Takato Hiranita, Francisco León, Lance R. McMahon, Christopher R. McCurdy. Novel Approaches, Drug Candidates, and Targets in Pain Drug Discovery. Journal of Medicinal Chemistry 2021, 64 (10) , 6523-6548. https://doi.org/10.1021/acs.jmedchem.1c00028
    7. Xianlei Wang, Shulin Wu, Junsheng Zuo, Keying Li, Yutong Chen, Zhijie Fan, Zhou Wu, Jun-Xia Yang, Weiyi Song, Jun-Li Cao, Mengqiao Cui. Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice. Communications Biology 2025, 8 (1) https://doi.org/10.1038/s42003-025-07590-2
    8. Mohammad M. Ibrahim, Mohamad Nurul Azmi, Maram B. Alhawarri, Nik Nur Syazni Nik Mohamed Kamal, Hasan AbuMahmoud. Synthesis, characterization and bioactivity of new pyridine-2(H)-one, nicotinonitrile, and furo[2,3-b]pyridine derivatives. Molecular Diversity 2025, 29 (2) , 1569-1587. https://doi.org/10.1007/s11030-024-10934-5
    9. Edward T. Ledingham, Johannes Puschnig, Ben W. Greatrex. Stereoselective access to bioactive cyclopropanes (+)-PPCC and (1R,2S)-2-aminomethyl-1-arylcyclopropane-1-carboxamides from (−)-levoglucosenone. Tetrahedron Letters 2025, 38 , 155620. https://doi.org/10.1016/j.tetlet.2025.155620
    10. Lile Jiang, Shujun Yang, Cuilian Zhang. Sigma‐1 Receptor‐Mediated High Mobility Group A1 Silencing Alleviates Endoplasmic Reticulum Stress‐Induced Ovarian Granulosa Cell Apoptosis: An In Vitro Cell Experimental Study. BJOG: An International Journal of Obstetrics & Gynaecology 2025, 132 (S2) , 120-131. https://doi.org/10.1111/1471-0528.18081
    11. Na Ye, Qi Wang, Yue Li, Xuechu Zhen. Current emerging therapeutic targets and clinical investigational agents for schizophrenia: Challenges and opportunities. Medicinal Research Reviews 2025, 45 (2) , 755-787. https://doi.org/10.1002/med.22086
    12. Giuseppe Cosentino, Maria Dichiara, Giuliana Costanzo, Alessandro Coco, Lorella Pasquinucci, Agostino Marrazzo, Antonio Rescifina, Emanuele Amata. Design and Synthesis of Tetrahydropyrrolo[3,4‐ c ]Pyrazole Sigma‐1 Receptor Ligands. ChemMedChem 2025, 15 https://doi.org/10.1002/cmdc.202401015
    13. Giuseppe Cosentino, Maria Dichiara, Francesca Alessandra Ambrosio, Claudia Giovanna Leotta, Giosuè Costa, Francesca Procopio, Giuliana Costanzo, Alessandro Raffa, Antonia Artacho-Cordón, M. Carmen Ruiz-Cantero, Lorella Pasquinucci, Agostino Marrazzo, Giovanni Mario Pitari, Enrique J. Cobos, Stefano Alcaro, Emanuele Amata. Development of selective sigma-1 receptor ligands with antiallodynic activity: A focus on piperidine and piperazine scaffolds. European Journal of Medicinal Chemistry 2025, 281 , 117037. https://doi.org/10.1016/j.ejmech.2024.117037
    14. Zbigniew Gajda, Magdalena Hawrylak, Jadwiga Handzlik, Kamil J. Kuder. Perry Disease: Current Outlook and Advances in Drug Discovery Approach to Symptomatic Treatment. International Journal of Molecular Sciences 2024, 25 (19) , 10652. https://doi.org/10.3390/ijms251910652
    15. Selvakumari Selvaraj, Muthu Sambantham, Manikandan Ayyar, Shine Kadaikunnan, Naiyf S. Alharbi. Molecular level interaction, molecular structure, chemical reactivity, electronic and topological exploration and docking studies of 1-acetyl-4-piperidinecarboxylic acid. Zeitschrift für Physikalische Chemie 2024, 238 (9) , 1705-1729. https://doi.org/10.1515/zpch-2023-0543
    16. Khadija Tarmoun, Véronik Lachance, Victoria Le Corvec, Sara-Maude Bélanger, Guillaume Beaucaire, Saïd Kourrich. Comprehensive Analysis of Age- and Sex-Related Expression of the Chaperone Protein Sigma-1R in the Mouse Brain. Brain Sciences 2024, 14 (9) , 881. https://doi.org/10.3390/brainsci14090881
    17. Gu-fang Zhang, Kai-lian Zhu, Qi Li, Yue Zhang, John L. Waddington, Xiang-dong Du, Xue-chu Zhen. The classical D1 dopamine receptor antagonist SCH23390 is a functional sigma-1 receptor allosteric modulator. Acta Pharmacologica Sinica 2024, 45 (8) , 1582-1590. https://doi.org/10.1038/s41401-024-01256-1
    18. Wen-Di Ge, Tian-Tian Du, Cao-Yang Wang, Lu-Ning Sun, Yong-Qing Wang. Calcium signaling crosstalk between the endoplasmic reticulum and mitochondria, a new drug development strategies of kidney diseases. Biochemical Pharmacology 2024, 225 , 116278. https://doi.org/10.1016/j.bcp.2024.116278
    19. Monika Sharma, Pankaj Pal, Sukesh Kumar Gupta. Advances in Alzheimer's disease: A multifaceted review of potential therapies and diagnostic techniques for early detection. Neurochemistry International 2024, 177 , 105761. https://doi.org/10.1016/j.neuint.2024.105761
    20. Maroua Fattouche, Salah Belaidi, Mebarka Ouassaf, Samir Chtita, Muneerah Mogren Al-Mogren, Majdi Hochlaf. Computational studies of pyrimidine derivatives as inhibitors of human σ1 receptor using 3D-QSAR analysis, molecular docking, ADMET properties and DFT investigation. Chemical Physics Impact 2024, 8 , 100463. https://doi.org/10.1016/j.chphi.2024.100463
    21. Grant D. Walby, Qi Gu, Hongfen Yang, Stephen F. Martin. Structure-Affinity relationships of novel σ2R/TMEM97 ligands. Bioorganic Chemistry 2024, 145 , 107191. https://doi.org/10.1016/j.bioorg.2024.107191
    22. Hui Ma, Jin-feng Li, Xin Qiao, Yue Zhang, Xiao-juan Hou, Hai-xia Chang, Hong-lei Chen, Yong Zhang, Yun-feng Li. Sigma-1 receptor activation mediates the sustained antidepressant effect of ketamine in mice via increasing BDNF levels. Acta Pharmacologica Sinica 2024, 45 (4) , 704-713. https://doi.org/10.1038/s41401-023-01201-8
    23. Sundas Tariq, Fazal Rahim, Hayat Ullah, Maliha Sarfraz, Rafaqat Hussain, Shoaib Khan, Misbah Ullah Khan, Wajid Rehman, Amjad Hussain, Mashooq Ahmad Bhat, Muhammad Kamran Farooqi, Syed Adnan Ali Shah, Naveed Iqbal. Synthesis, In Vitro Biological Evaluation and Molecular Modeling of Benzimidazole-Based Pyrrole/Piperidine Hybrids Derivatives as Potential Anti-Alzheimer Agents. Pharmaceuticals 2024, 17 (4) , 410. https://doi.org/10.3390/ph17040410
    24. Zhiyuan Fan, Yang Xiao, Yuxin Shi, Chao Hao, Yin Chen, Guisen Zhang, Tao Zhuang, Xudong Cao. Thiophenpiperazine amide derivatives as new dual MOR and σ1R ligands for the treatment of pain. Biochemical and Biophysical Research Communications 2024, 697 , 149547. https://doi.org/10.1016/j.bbrc.2024.149547
    25. Yukitoshi Izumi, Angela M. Reiersen, Eric J. Lenze, Steven J. Mennerick, Charles F. Zorumski. SSRIs differentially modulate the effects of pro-inflammatory stimulation on hippocampal plasticity and memory via sigma 1 receptors and neurosteroids. Translational Psychiatry 2023, 13 (1) https://doi.org/10.1038/s41398-023-02343-3
    26. Nhi T. Nguyen, Valeria Jaramillo-Martinez, Marilyn Mathew, Varshini V. Suresh, Sathish Sivaprakasam, Yangzom D. Bhutia, Vadivel Ganapathy. Sigma Receptors: Novel Regulators of Iron/Heme Homeostasis and Ferroptosis. International Journal of Molecular Sciences 2023, 24 (19) , 14672. https://doi.org/10.3390/ijms241914672
    27. Laura De Luca, Lisa Lombardo, Salvatore Mirabile, Agostino Marrazzo, Maria Dichiara, Giuseppe Cosentino, Emanuele Amata, Rosaria Gitto. Discovery and computational studies of piperidine/piperazine-based compounds endowed with sigma receptor affinity. RSC Medicinal Chemistry 2023, 14 (9) , 1734-1742. https://doi.org/10.1039/D3MD00291H
    28. Zheng Ying, Na Ye, Qilian Ma, Fan Chen, Ningning Li, Xuechu Zhen. Targeted to neuronal organelles for CNS drug development. Advanced Drug Delivery Reviews 2023, 200 , 115025. https://doi.org/10.1016/j.addr.2023.115025
    29. Yan Lu, Qi Gu, Stephen F. Martin. Structure-affinity relationships of stereoisomers of norbenzomorphan-derived σ2R/TMEM97 modulators. European Journal of Medicinal Chemistry 2023, 257 , 115488. https://doi.org/10.1016/j.ejmech.2023.115488
    30. Damian J. Woodward, Jackson G. Thorp, Wole Akosile, Jue-Sheng Ong, Eric R. Gamazon, Eske M. Derks, Zachary F. Gerring. Identification of drug repurposing candidates for the treatment of anxiety: A genetic approach. Psychiatry Research 2023, 326 , 115343. https://doi.org/10.1016/j.psychres.2023.115343
    31. Tao Wang, Hongmei Jia. The Sigma Receptors in Alzheimer’s Disease: New Potential Targets for Diagnosis and Therapy. International Journal of Molecular Sciences 2023, 24 (15) , 12025. https://doi.org/10.3390/ijms241512025
    32. Mallory Burns, Nicholas Guadagnoli, Christopher R. McCurdy. Advances with the discovery and development of novel sigma 1 receptor antagonists for the management of pain. Expert Opinion on Drug Discovery 2023, 18 (7) , 693-705. https://doi.org/10.1080/17460441.2023.2216015
    33. Judit Hodrea, Minh Ngoc Tran, Balazs Besztercei, Timea Medveczki, Attila J. Szabo, Laszlo Őrfi, Illes Kovacs, Andrea Fekete. Sigma-1 Receptor Agonist Fluvoxamine Ameliorates Fibrotic Response of Trabecular Meshwork Cells. International Journal of Molecular Sciences 2023, 24 (14) , 11646. https://doi.org/10.3390/ijms241411646
    34. Jing Zhao, Rajalakshmi Veeranan-Karmegam, Frederick C. Baker, Barbara A. Mysona, Pritha Bagchi, Yutao Liu, Sylvia B. Smith, Graydon B. Gonsalvez, Kathryn E. Bollinger. Defining the ligand-dependent proximatome of the sigma 1 receptor. Frontiers in Cell and Developmental Biology 2023, 11 https://doi.org/10.3389/fcell.2023.1045759
    35. Peng Ren, Jing-Ya Wang, Hong-Lei Chen, Hai-Xia Chang, Zhi-Rui Zeng, Guang-Xiang Li, Hui Ma, Yong-Qi Zhao, Yun-Feng Li. Sigma-1 receptor agonist properties that mediate the fast-onset antidepressant effect of hypidone hydrochloride (YL-0919). European Journal of Pharmacology 2023, 946 , 175647. https://doi.org/10.1016/j.ejphar.2023.175647
    36. Kequan Fu, Wen Xu, Ruicong Yang, Huimin Zhao, Huanyu Xu, Yaqin Wei, Hongli Liu, Yinli Qiu, Danqi Chen, Dong Guo, Bing Xiong. 2,6-diazaspiro[3.4]octan-7-one derivatives as potent sigma-1 receptor antagonists that enhanced the antinociceptive effect of morphine and rescued morphine tolerance. European Journal of Medicinal Chemistry 2023, 249 , 115178. https://doi.org/10.1016/j.ejmech.2023.115178
    37. Véronik Lachance, Sara-Maude Bélanger, Célia Hay, Victoria Le Corvec, Vina Banouvong, Mathieu Lapalme, Khadija Tarmoun, Guillaume Beaucaire, Marc P. Lussier, Saïd Kourrich. Overview of Sigma-1R Subcellular Specific Biological Functions and Role in Neuroprotection. International Journal of Molecular Sciences 2023, 24 (3) , 1971. https://doi.org/10.3390/ijms24031971
    38. Francisco Javier Munguia-Galaviz, Alejandra Guillermina Miranda-Diaz, Miguel Alejandro Cardenas-Sosa, Raquel Echavarria. Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases. International Journal of Molecular Sciences 2023, 24 (3) , 1997. https://doi.org/10.3390/ijms24031997
    39. Nikita A. Frolov, Anatoly N. Vereshchagin. Piperidine Derivatives: Recent Advances in Synthesis and Pharmacological Applications. International Journal of Molecular Sciences 2023, 24 (3) , 2937. https://doi.org/10.3390/ijms24032937
    40. Jing Li, Kenneth A. Satyshur, Lian-Wang Guo, Arnold E. Ruoho. Sphingoid Bases Regulate the Sigma-1 Receptor—Sphingosine and N,N’-Dimethylsphingosine Are Endogenous Agonists. International Journal of Molecular Sciences 2023, 24 (4) , 3103. https://doi.org/10.3390/ijms24043103
    41. Christian Behl. “If You Change the Way You Look at Things, Things You Look at Change”. 2023, 575-635. https://doi.org/10.1007/978-3-031-31570-1_21
    42. Leonid I. Belen’kii, Galina A. Gazieva, Yulia B. Evdokimenkova, Natalya O. Soboleva. The literature of heterocyclic chemistry, Part XX, 2020. 2023, 201-274. https://doi.org/10.1016/bs.aihch.2022.10.005
    43. Kim I. Bishop, Peter K. Isquith, Gerard A. Gioia, Kelly G. Knupp, Ingrid E. Scheffer, Rima Nabbout, Nicola Specchio, Joseph Sullivan, Stéphane Auvin, J. Helen Cross, Renzo Guerrini, Gail Farfel, Bradley S. Galer, Arnold R. Gammaitoni. Fenfluramine treatment is associated with improvement in everyday executive function in preschool-aged children (<5 years) with Dravet syndrome: A critical period for early neurodevelopment. Epilepsy & Behavior 2023, 138 , 108994. https://doi.org/10.1016/j.yebeh.2022.108994
    44. Mengyu Du, Tao Jiang, Shuxuan He, Bo Cheng, Xin Zhang, Liya Li, Lan Yang, Wei Gao, Yansong Li, Qiang Wang. Sigma-1 Receptor as a Protective Factor for Diabetes-Associated Cognitive Dysfunction via Regulating Astrocytic Endoplasmic Reticulum-Mitochondrion Contact and Endoplasmic Reticulum Stress. Cells 2023, 12 (1) , 197. https://doi.org/10.3390/cells12010197
    45. Kirsten T. Tolentino, Viktoriya Mashinson, Manish K. Sharma, Yashpal S. Chhonker, Daryl J. Murry, Corey R. Hopkins. From dopamine 4 to sigma 1: Synthesis, SAR and biological characterization of a piperidine scaffold of σ1 modulators. European Journal of Medicinal Chemistry 2022, 244 , 114840. https://doi.org/10.1016/j.ejmech.2022.114840
    46. Antonino N. Fallica, Valeria Ciaffaglione, Maria N. Modica, Valeria Pittalà, Loredana Salerno, Emanuele Amata, Agostino Marrazzo, Giuseppe Romeo, Sebastiano Intagliata. Structure-activity relationships of mixed σ1R/σ2R ligands with antiproliferative and anticancer effects. Bioorganic & Medicinal Chemistry 2022, 73 , 117032. https://doi.org/10.1016/j.bmc.2022.117032
    47. Bénédicte Oxombre, Fahima Madouri, Anne-Sophie Journé, Séverine Ravez, Eloise Woitrain, Pascal Odou, Nathalie Duhal, Sandro Ninni, David Montaigne, Nadira Delhem, Patrick Vermersch, Patricia Melnyk. Safe and Efficient Sigma1 Ligand: A Potential Drug Candidate for Multiple Sclerosis. International Journal of Molecular Sciences 2022, 23 (19) , 11893. https://doi.org/10.3390/ijms231911893
    48. Héctor M. Estévez-Silva, Germán Cuesto, Ninovska Romero, José Miguel Brito-Armas, Abraham Acevedo-Arozena, Ángel Acebes, Daniel J. Marcellino. Pridopidine Promotes Synaptogenesis and Reduces Spatial Memory Deficits in the Alzheimer's Disease APP/PS1 Mouse Model. Neurotherapeutics 2022, 19 (5) , 1566-1587. https://doi.org/10.1007/s13311-022-01280-1
    49. Nicolas Levoin, Appala Venkata Ramana Murthy, Vennu Narendar, Nangunoori Sampath Kumar, Pasula Aparna, Anagani Kanaka Durga Bhavani, Chada Raji Reddy, Paul Mosset, René Grée. Discovery of potent dual ligands for dopamine D4 and σ1 receptors. Bioorganic & Medicinal Chemistry 2022, 69 , 116851. https://doi.org/10.1016/j.bmc.2022.116851
    50. Tao Wang, Ying Zhang, Xiaojun Zhang, Leyuan Chen, Mingqiang Zheng, Jinming Zhang, Peter Brust, Winnie Deuther-Conrad, Yiyun Huang, Hongmei Jia. Synthesis and characterization of the two enantiomers of a chiral sigma-1 receptor radioligand: (S)-(+)- and (R)-(-)-[18F]FBFP. Chinese Chemical Letters 2022, 33 (7) , 3543-3548. https://doi.org/10.1016/j.cclet.2022.03.099
    51. Peng Ren, Jingya Wang, Nanxi Li, Guangxiang Li, Hui Ma, Yongqi Zhao, Yunfeng Li. Sigma-1 Receptors in Depression: Mechanism and Therapeutic Development. Frontiers in Pharmacology 2022, 13 https://doi.org/10.3389/fphar.2022.925879
    52. Ryan S. D’Souza, Brendan Langford, Rachel E. Wilson, Yeng F. Her, Justin Schappell, Jennifer S. Eller, Timothy C. Evans, Jonathan M. Hagedorn. The state-of-the-art pharmacotherapeutic options for the treatment of chronic non-cancer pain. Expert Opinion on Pharmacotherapy 2022, 23 (7) , 775-789. https://doi.org/10.1080/14656566.2022.2060741
    53. Catharina Holtschulte, Frederik Börgel, Stefanie Westphälinger, Dirk Schepmann, Gianluca Civenni, Erik Laurini, Domenico Marson, Carlo V. Catapano, Sabrina Pricl, Bernhard Wünsch. Synthesis of Aminoethyl‐Substituted Piperidine Derivatives as σ 1 Receptor Ligands with Antiproliferative Properties. ChemMedChem 2022, 17 (7) https://doi.org/10.1002/cmdc.202100735
    54. Piotr F. J. Lipiński, Joanna Matalińska. Fentanyl Structure as a Scaffold for Opioid/Non-Opioid Multitarget Analgesics. International Journal of Molecular Sciences 2022, 23 (5) , 2766. https://doi.org/10.3390/ijms23052766
    55. Maria Dichiara, Antonia Artacho-Cordón, Rita Turnaturi, Miriam Santos-Caballero, Rafael González-Cano, Lorella Pasquinucci, Carla Barbaraci, Isabel Rodríguez-Gómez, Manuel Gómez-Guzmán, Agostino Marrazzo, Enrique J. Cobos, Emanuele Amata. Dual Sigma-1 receptor antagonists and hydrogen sulfide-releasing compounds for pain treatment: Design, synthesis, and pharmacological evaluation. European Journal of Medicinal Chemistry 2022, 230 , 114091. https://doi.org/10.1016/j.ejmech.2021.114091
    56. Laura R. Rodríguez, Tamara Lapeña-Luzón, Noelia Benetó, Vicent Beltran-Beltran, Federico V. Pallardó, Pilar Gonzalez-Cabo, Juan Antonio Navarro. Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases?. Antioxidants 2022, 11 (1) , 165. https://doi.org/10.3390/antiox11010165
    57. Tao Zhuang, Jiaying Xiong, Shuaishuai Hao, Wei Du, Zhenming Liu, Bifeng Liu, Guisen Zhang, Yin Chen. Bifunctional μ opioid and σ1 receptor ligands as novel analgesics with reduced side effects. European Journal of Medicinal Chemistry 2021, 223 , 113658. https://doi.org/10.1016/j.ejmech.2021.113658
    58. Szabolcs Dvorácskó, László Lázár, Ferenc Fülöp, Márta Palkó, Zita Zalán, Botond Penke, Lívia Fülöp, Csaba Tömböly, Ferenc Bogár. Novel High Affinity Sigma-1 Receptor Ligands from Minimal Ensemble Docking-Based Virtual Screening. International Journal of Molecular Sciences 2021, 22 (15) , 8112. https://doi.org/10.3390/ijms22158112
    59. Parthena Martin, Thadd Reeder, Jo Sourbron, Peter A. M. de Witte, Arnold R. Gammaitoni, Bradley S. Galer. An Emerging Role for Sigma-1 Receptors in the Treatment of Developmental and Epileptic Encephalopathies. International Journal of Molecular Sciences 2021, 22 (16) , 8416. https://doi.org/10.3390/ijms22168416
    60. Lin Guo, Tianyu Gao, Ce Gao, Xiaoxia Jia, Jing Ni, Chaojun Han, Yun Wang. Stimulation of astrocytic sigma-1 receptor is sufficient to ameliorate inflammation- induced depression. Behavioural Brain Research 2021, 410 , 113344. https://doi.org/10.1016/j.bbr.2021.113344
    61. Vladimir Zhemkov, Michal Geva, Michael R. Hayden, Ilya Bezprozvanny. Sigma-1 Receptor (S1R) Interaction with Cholesterol: Mechanisms of S1R Activation and Its Role in Neurodegenerative Diseases. International Journal of Molecular Sciences 2021, 22 (8) , 4082. https://doi.org/10.3390/ijms22084082
    Download PDF
    Go to Journal of Medicinal Chemistry
    Get e-Alerts
    Get e-Alerts

    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2020, 63, 24, 15187–15217
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jmedchem.0c01192
    Published October 28, 2020
    Copyright © 2020 American Chemical Society
    Request reuse permissions

    Article Views

    4909

    Altmetric

    -

    Citations

    61
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.