Sigma-2 receptor

Published research to date related to the Sigma-2 protein (TMEM97) has been conducted with compounds not developed by Advantx Pharmaceuticals Inc. Our therapeutic candidate ADV462 is the first truly selective, pharmaceutical-grade compound in development targeting the Sigma-2 receptor with a novel. and clean molecule with unambiguous antagonist activity, far superior in potency, selectivity, safety, and efficacy to all others tested to date.

RECENT SCIENTIFIC PUBLICATIONS RELATED TO THE SIGMA-2 PROTEIN

Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer’s disease

By Martí Colom-Cadena, Jamie Toombs, Elizabeth Simzer, Kristjan Holt, Robert McGeachan, Jane Tulloch, Rosemary J. Jackson, James H. Catterson, Maxwell P. Spires-Jones, Jamie Rose, Lora Waybright, Anthony O. Caggiano, Declan King, Francesco Gobbo, Caitlin Davies, Monique Hooley, Sophie Dunnett, Robert Tempelaar, Soraya Meftah, Makis Tzioras, Mary E. Hamby, Nicholas J. Izzo, Susan M. Catalano, Claire […]

Highly specific σ2R/TMEM97 ligand FEM-1689 alleviates neuropathic pain and inhibits the integrated stress response

By Muhammad Saad Yousuf, James J. Sahn, Hongfen Yang, Eric T. David, Stephanie Shiers, Marisol Mancilla Moreno, Jonathan Iketem, Danielle M. Royer, Chelsea D. Garcia, Jennifer Zhang, Veronica M. Hong, Subhaan M. Mian, Ayesha Ahmad, Benedict J. Kolber, Daniel J. Liebl, Stephen F. Martin, and Theodore J. Price Excerpt from the article published in Proceedings […]

TMEM97/Sigma 2 Receptor Increases Estrogen Receptor α Activity in Promoting Breast Cancer Cell Growth

By Yuanqin Zhang, Xiangwei Fang, Jiuhui Wang and Daotai Nie Excerpt from the article published in Cancers 2023, 15(23): 5691. 2 December 2023. DOI: https://doi.org/10.3390/cancers15235691 Editor’s Highlitghts Simple Summary Selective estrogen receptor modulators are a major treatment modality for estrogen receptor-positive breast cancers, but the emergence of resistance or a lack of initial responsiveness is a […]

Sigma Receptor Ligands Prevent COVID Mortality In Vivo: Implications for Future Therapeutics

By Reed L. Berkowitz, Andrew P. Bluhm, Glenn W. Knox, Christopher R. McCurdy, David A. Ostrov, and Michael H. Norris Excerpt from the article published in  International Journal of Molecular Sciences. 29 October 2023; 24(21):15718. DOI: https://doi.org/10.3390/ijms242115718 Editor’s Highlights Abstract The emergence of lethal coronaviruses follows a periodic pattern which suggests a recurring cycle of […]

Sigma Receptors: Novel Regulators of Iron/Heme Homeostasis and Ferroptosis

By Nhi T. Nguyen, Valeria Jaramillo-Martinez, Marilyn Mathew, Varshini V. Suresh, Sathish Sivaprakasam, Yangzom D. Bhutia, and Vadivel Ganapathy Excerpt from the article published in International Journal of Molecular Sciences.  28 September 2023; 24(19):14672. DOI: https://doi.org/10.3390/ijms241914672 Editor’s Higlights Abstract Sigma receptors are non-opiate/non-phencyclidine receptors that bind progesterone and/or heme and also several unrelated xenobiotics/chemicals. They […]

BS148 Reduces the Aggressiveness of Metastatic Melanoma via Sigma-2 Receptor Targeting

By Claudia Sorbi, Silvia Belluti, Claudio Giacinto Atene, Federica Marocchi, Pasquale Linciano, Neena Roy, Elia Paradiso, Livio Casarini, Simone Ronsisvalle, Tommaso Zanocco-Marani, Livio Brasili, Luisa Lanfrancone, Carol Imbriano, Giulia Di Rocco, and Silvia Franchini Excerpt from the article published in the International Journal of Molecular Sciences. 2 June 2023; 24(11):9684. DOI: https://doi.org/10.3390/ijms24119684 Editor’s Highlights Abstract […]

Validation of σ2R/TMEM97 as a neuropathic pain target: Specificity, human expression and mechanism of action

By Muhammad Saad Yousuf, James J. Sahn, Eric T. David, Stephanie Shiers, Danielle M. Royer, Chelsea D. Garcia, Jennifer Zhang, Veronica M. Hong, Ayesha Ahmad, Benedict J. Kolber, Daniel J Liebl, Stephen F. Martin, and Theodore J. Price Excerpt from the article published in bioRxiv 2023.04.11., 536439;  DOI: https://doi.org/10.1101/2023.04.11.536439 Editor’s Highlights Abstract The Sigma 2 receptor (σ2R) […]

Sigma-2 Receptor Ligand Binding Modulates Association between TSPO and TMEM97

By Bashar M. Thejer, Vittoria Infantino, Anna Santarsiero, Ilaria Pappalardo, Francesca S. Abatematteo, Sarah Teakel, Ashleigh Van Oosterum, Robert H. Mach, Nunzio Denora, Byung Chul Lee, Nicoletta Resta, Rosanna Bagnulo, Mauro Niso, Marialessandra Contino, Bianca Montsch, Petra Heffeter, Carmen Abate, and Michael A. Cahill Excerpt from the article published in the International Journal of Molecular […]

Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases

By Britney N. Lizama, Jennifer Kahle, Susan M. Catalano, Anthony O. Caggiano, Michael Grundman, and Mary E. Hamby Excerpt from the article published in the International Journal of Molecular Sciences. 24(7):6251. 26 March 2023. DOI: https://doi.org/10.3390/ijms24076251 Editor’s Highlights Abstract There is a large unmet medical need to develop disease-modifying treatment options for individuals with age-related […]

Development of a CRISPRi Human Retinal Pigmented Epithelium Model for Functional Study of Age-Related Macular Degeneration Genes

By Jiang-Hui Wang, Daniel Urrutia-Cabrera, Jarmon G. Lees, Santiago Mesa Mora, Tu Nguyen, Sandy S. C. Hung, Alex W. Hewitt, Shiang Y. Lim, Thomas L. Edwards, and Raymond C. B. Wong Excerpt from the article published in the International Journal of Molecular Sciences. 8 February 2023; 24(4):3417. DOI: https://doi.org/10.3390/ijms24043417 Editor’s Highlights Abstract Age-related macular degeneration […]

Retinal Photoreceptor Protection in an AMD-Related Mouse Model by Selective Sigma-1 or Sigma-2 Receptor Modulation

By Timur A. Mavlyutov, Jing Li, Xinying Liu, Hongtao Shen, Huan Yang, Christopher R. McCurdy, Bikash Pattnaik, and Lian-Wang Guo Excerpt from the article published in Genes 13(12):2386, 16 December 2022, DOI: https://doi.org/10.3390/genes13122386 Editor’s Highlights Abstract The structurally and genetically distinct sigma-1 receptor (S1R) and sigma-2 receptor (S2R) comprise a unique class of drug binding […]

σ2R/TMEM97 in retinal ganglion cell degeneration

By Hua Wang, Zhiyou Peng, Yiwen Li, James J. Sahn, Timothy R. Hodges, Tsung-Han Chou, Qiong Liu, Xuezhi Zhou, Shuliang Jiao, Vittorio Porciatti, Daniel J. Liebl, Stephen F. Martin, and Rong Wen Excerpt from the article published in Scientific Reports 12, 20753, 01 December 2022, DOI: https://doi.org/10.1038/s41598-022-24537-3 Editor’s Highlights Abstract The sigma 2 receptor (σ2R) […]

(–)-Epicatechin Provides Neuroprotection in Sodium Iodate-Induced Retinal Degeneration

By Manjuan Peng, Xuezhi Zhou, Fei Yao, Haibo Li, Weitao Song, Siqi Xiong, and Xiaobo Xia Excerpt from the article published in Frontiers in Medicine, volume 9, 27 June 2022, DOI: https://doi.org/10.3389/fmed.2022.879901 Editor’s Highlights Dry age-related macular degeneration (AMD) accounts for approximately 5.8% of legal blindness globally and is the leading cause of severe vision […]

Amyloid Cascade Hypothesis for the Treatment of Alzheimer’s Disease: Progress and Challenges

By Tong Wu , Ding Lin , Yaqian Cheng , Senze Jiang , Muhammad Waheed Riaz , Nina Fu , Chenhao Mou , Menglu Ye , and Ying Zheng.  Excerpt from the article published in Aging and disease. 2022. Doi: 10.14336/AD.2022.0412 Editor’s Highlights Nowadays, the significance and complexity of the amyloid cascade hypothesis in the development of Alzheimer’s disease have been undisputed. The origin of the Aβ pathogenic pathway is mostly considered […]

Sigma 2 receptor (σ2R/TMEM97) in Retinal Ganglion Cell Degeneration

By Hua Wang, Zhiyou Peng, Yiwen Li et al. Excerpt from the article published in Retinal Ganglion Cell Degeneration, 15 March 2022, PREPRINT (Version 1) available at Research Square Doi: https://doi.org/10.21203/rs.3.rs-1439890/v1 Editor’s Highlights The sigma 2 receptor (σ2R) plays a signicant role in the retinal ganglion cell (RGC) degeneration pathway and that inhibiting σ2R/TMEM97 function is […]

BRD2 regulation of sigma-2 receptor upon cholesterol deprivation

By Hongtao Shen, Jing Li, Xiujie Xie, Huan Yang, Mengxue Zhang, Bowen Wang, K Craig Kent, Jorge Plutzky, and Lian-Wang GuoLife Excerpt from the article published in Science Alliance Nov 2020, 4 (1) e201900540; DOI: 10.26508/lsa.201900540 Editor’s Highlights Sigma-2 receptor is a recently unveiled player in cholesterol homeostasis. Bromodomain BRD2 and SREBP2 (sterol regulatory element-binding protein 2) cooperatively regulates S2R transcription. […]

A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes

By Yu-Shiuan Cheng, Tianyi Zhang, Xiang Ma, Sarida Pratuangtham, Grace C. Zhang, Alexander A. Ondrus, Amirhossein Mafi, Brett Lomenick, Jeffrey J. Jones, and Alison E. Ondrus Excerpt from the author manuscript published in Nature Chemical Biology 17, 1271–1280 (19 November 2021 DOI: https://doi.org/10.1038/s41589-021-00907-2 Editor’s Highlights Oxysterols (OHCs) are hydroxylated cholesterol metabolites that play ubiquitous roles in health […]

The Sigma-2 Receptor/TMEM97 Agonist PB28 Suppresses Cell Proliferation and Invasion by Regulating the PI3K-AKT-mTOR Signalling Pathway in Renal Cancer

By Bo Zhan, Zhe Zhang, Chiyuan Piao, Xiao Dong, Yang Du, Chuize Kong, and Yuanjun Jiang Excerpt from the article published in the Journal of Cellular and Molecular Medicine, 16 November 2021 https://doi.org/10.1111/jcmm.17047 Editor’s Highlights Renal cancer is a malignancy that increases the burden of human cancers and has a poor prognosis rate, and there are […]

Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells

by Ostrov, D.A.; Bluhm, A.P.;Li, D.; Khan, J.Q.; Rohamare, M.;Rajamanickam, K.; K. Bhanumathy,K.; Lew, J.; Falzarano, D.;Vizeacoumar, F.J.; et al. Excerpt from the article published in Pathogens 2021,10, 1514. https://doi.org/10.3390/pathogens10111514 Editor’s Highlights Background There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants […]

PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones

By Yu-Jie Chen, Jeffrey Knupp, Anoop Arunagiri, Leena Haataja, Peter Arvan, and Billy Tsai Excerpt from the article published in Nature Communications 12, 5991 (2021), 13 October 2021, DOI: https://doi.org/10.1038/s41467-021-26225-8 Editor’s Highlights Protein misfolding in the endoplasmic reticulum (ER) causes a myriad of human diseases, including neurodegenerative diseases, cancer, and diabetes. Amongst the most well characterized of […]

Multifunctional thiosemicarbazones targeting sigma receptors: in vitro and in vivo antitumor activities in pancreatic cancer models

By Mauro Niso, Joanna Kopecka, Francesca Serena Abatematteo, Francesco Berardi, Chiara Riganti, and Carmen Abate Excerpt from the article published in Cellular Oncology 44, 1307–1323 (2021). https://doi.org/10.1007/s13402-021-00638-5 Editor’s Highlights Pancreatic cancer is one of the most aggressive forms of cancer characterized by a poor prognosis and a five-year survival rate of ~ 8 %.  Surgery represents the […]

Crystal structures of the σ2 receptor template large-library docking for selective chemotypes active in vivo

By Assaf Alon, Jiankun Lyu, Joao M. Braz, Tia A. Tummino, Veronica Craik, Matthew J.O’Meara, Chase M. Webb, Dmytro S. Radchenko, Yurii S. Moroz, Xi-Ping Huang, Yongfeng Liu, Bryan L. Roth, John J. Irwin, Allan I. Basbaum, Brian K. Shoichet, and Andrew C. Kruse Excerpt from the article published in bioRxiv 2021.04.29.441652; April 30, 2021; DOI: https://doi.org/10.1101/2021.04.29.441652 Editor’s Highlights Abstract The σ2 receptor is a poorly understood transmembrane receptor that has attracted intense interest in many areas of biology including cancer imaging, Alzheimer’s disease, schizophrenia, and neuropathic pain. However, […]

The ER protein Ema19 [tmem97] facilitates the degradation of nonimported mitochondrial precursor proteins

By Janina Laborenz, Yury S. Bykov, Katharina Knöringer, Markus Räschle, Sabine Filker, Cristina Prescianotto-Baschong, Anne Spang, Takashi Tatsuta, Thomas Langer, Zuzana Storchová, Maya Schuldiner, and Johannes M. Herrmann Excerpt from the article published on Molecular Biology of the Cell, Volume 32, Issue 8, Published Online: 13 Apr 2021, DOI: https://doi.org/10.1091/mbc.E20-11-0748 Editor’s Highlights Ema19 is the […]

The Sigma-2 Receptor / Transmembrane protein 97 (σ2R/TMEM97) Modulator JVW-1034 Reduces Heavy Alcohol Drinking and Associated Pain States in Male Mice

By Sema G. Quadir, Sean M. Tanino, Christian D. Rohl, James J. Sahn, Emily J. Yao, Luíza dos Reis Cruz, Pietro Cottone, Stephen F. Martin, and Valentina Sabino Excerpt from the article published in Neuropharmacology, Volume 184, 108409, 15 February 2021. DOI: https://doi.org/10.1016/j.neuropharm.2020.108409. Author manuscript available at NCBI HHS public access: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856185/ Editor’s Highlights Abstract Alcohol Use Disorder […]

TMEM97 increases in synapses and is a potential synaptic Aβ binding partner in human Alzheimer’s disease

By Martí Colom-Cadena, Jane Tulloch, Rosemary J Jackson, James H Catterson, Jamie Rose, Caitlin Davies, Monique Hooley, Alejandro Anton-Fernandez, Sophie Dunnett, Robert Tempelaar, Makis Tzioras, Nicholas J Izzo, Susan M. Catalano, Colin Smith, and Tara L. Spires-Jones Excerpt from the article published in bioRxiv 2021.02.01, 428238; DOI: https://doi.org/10.1101/2021.02.01.428238 Editor’s Highlights Abstract Synapse loss correlates with cognitive decline in […]

Sigma-2 receptor antagonists rescue neuronal dysfunction induced by Parkinson’s patient brain-derived α-synuclein

By Colleen S. Limegrover, Raymond Yurko, Nicholas J. Izzo, Kelsie M. LaBarbera, Courtney Rehak, Gary Look, Gilbert Rishton, Hank Safferstein, and Susan M. Catalano Excerpt from the article published in  Journals of Neuroscience Research; 99: 1161– 1176, 22 January 2021, DOI: https://doi.org/10.1002/jnr.24782 Editor’s Highlights Oligomeric α-synuclein proteins found in Parkinson’s disease patient brain tissue cause neuron dysfunction. α-synuclein […]

Sigma-2 Receptor—A Potential Target for Cancer/Alzheimer’s Disease Treatment via Its Regulation of Cholesterol Homeostasis

By Kai Yang, Cheng Zeng, Changcai Wang, Meng Sun, Dan Yin, and Taolei Sun Excerpt from the article published in Molecules 25, no. 22: 5439, 2020 https://doi.org/10.3390/molecules25225439 Editor’s Highlights Recently transmembrane protein 97 (TMEM97) was identified as a sigma-2 receptor identity using mass spectrometry after affinity purification from the liver. TMEM97/sigma-2 receptor forms a trimeric complex […]

The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception

By Sánchez-Blázquez, P., Cortés-Montero, E., Rodríguez-Muñoz, M. et al.  Excerpt from the article published in Mol Brain 13, 150 (2020). https://doi.org/10.1186/s13041-020-00676-4 Editor’s Highlights σ2R is essential for the antinociceptive effects of exogenous and endogenous ligands of MOR but not for the antinociceptive effects of other families of G-receptors that also mediate analgesia, such as DOR, CB1R and α2AR. […]

The Sigma-2 Receptor, PGRMC1, and LDL Receptor complex are responsible for the cellular uptake of Aβ42 and its protein aggregates

by Aladdin Riad, Zsofia Lengyel-Zhand, Chenbo Zeng, Chi-Chang Weng, Virginia M.-Y. Lee, John Q. Trojanowski, and Robert H. Mach Excerpt from the article published in final edited form as: Mol Neurobiol. 2020 September DOI: 10.1007/s12035-020-01988-1 Editor’s Highlights Sigma-2 receptor (TMEM97) and PGRMC1 are therapeutic targets for inhibiting neuronal uptake of Aβ42 and ApoE-associated Aβ42 and potentially […]

Sigma-2 receptor as a potential therapeutic target for treating central nervous system disorders

by Terada K, Migita K, Matsushima Y, Kamei C.  Excerpt from the article published in Neural Regen Res 2019;14:1893-4 DOI: 10.4103/1673-5374.259609 The sigma receptor (Sig-R) was first reported by Martin et al. (1976) and was initially classified into the opioid receptor family. However, Sig-R was subsequently found to differ from the opioid receptor in various studies […]

Sigma-2 Receptor/TMEM97 and PGRMC-1 Increase the Rate of Internalization of LDL by LDL Receptor through the Formation of a Ternary Complex

By Aladdin Riad, Chenbo Zeng, Chi-Chang Weng, Harrison Winters, Kuiying Xu, Mehran Makvandi, Tyler Metz, Sean Carlin, and Robert H. Mach Excerpt from the article published in Scientific Reports 8, 16845, 15 November 2018, DOI: https://doi.org/10.1038/s41598-018-35430-3 Editor’s Highlights The disruption of lipoprotein trafficking may also be responsible for the mechanism of action of sigma-2 receptors (TMEM97/σ2R) […]

Small molecule modulators of σ2R/Tmem97 reduce alcohol withdrawal-induced behaviors

By Luisa L. Scott, James J. Sahn, Antonio Ferragud, Rachel C. Yen, Praveen N. Satarasinghe, Michael D. Wood, Timothy R. Hodges, Ted Shi, Brooke A. Prakash, Kaitlyn M. Friese, Angela Shen, Valentina Sabino, Jonathan T. Pierce, and Stephen F. Martin Excerpt from the article published in Neuropsychopharmacol 43, 1867–1875, 20 April 2018, DOI: https://doi.org/10.1038/s41386-018-0067-z Editor’s Highlights […]

Cocaine Effects on Dopaminergic Transmission Depend on a Balance between Sigma-1 and Sigma-2 Receptor Expression

By David Aguinaga, Mireia Medrano, Ignacio Vega-Quiroga, Katia Gysling, Enric I. Canela, Gemma Navarro, and Rafael Franco Excerpt from the article published in Frontiers in Molecular Neuroscience, 12 February 2018, Sec. Molecular Signalling and Pathways, Volume 11 – 2018, DOI: https://doi.org/10.3389/fnmol.2018.00017 Editor’s Highlitghts Abstract Sigma σ1 and σ2 receptors are targets of cocaine. Despite sharing a similar name, the […]

The Sigma-2 Receptor Selective Agonist Siramesine (Lu 28-179) Decreases Cocaine-Reinforced Pavlovian Learning and Alters Glutamatergic and Dopaminergic Input to the Striatum

By Anna M. Klawonn, Anna Nilsson, Carl F. Rådberg, Sarah H. Lindström, Mia Ericson, Björn Granseth, David Engblom, and Michael Fritz Excerpt from the article published in Frontiers in Pharmacology, 10 October 2017, Sec. Experimental Pharmacology and Drug Discovery, Volume 8 – 2017, DOI: https://doi.org/10.3389/fphar.2017.00714 Editor’s Highlights Abstract Drug addiction is a chronic, debilitating disease that […]

Sigma 2 Receptor/Tmem97 Agonists Produce Long Lasting Antineuropathic Pain Effects in Mice

By James J Sahn, Galo L Mejia, Pradipta R Ray, Stephen F Martin, and Theodore J Price Excerpt from the article published in ACS chemical neuroscience, 2017 Aug 16;8(8):1801-1811. DOI: https://doi.org/10.1021/acschemneuro.7b00200 Free PMC article Editor’s Highlights Abstract Neuropathic pain is an important medical problem with few effective treatments. The sigma 1 receptor (σ1R) is known to be […]

Small molecule modulator of sigma 2 receptor is neuroprotective and reduces cognitive deficits and neuroinflammation in experimental models of Alzheimer’s disease

By Bitna Yi, James J. Sahn, Pooneh Memar Ardestani, Andrew K. Evans, Luisa L. Scott, Jessica Z. Chan, Sangeetha Iyer, Ashley Crisp, Gabriella Zuniga, Jonathan T. Pierce, Stephen F. Martin, and Mehrdad Shamloo Excerpt from the article published in  Journal of Neurochemistry, 07 December 2016, 140: 561-575. DOI: https://doi.org/10.1111/jnc.13917 Editor’s Highlights Abstract Accumulating evidence suggests that […]