Sigma and Metabolic Diseases

Published research to date related to Sigma proteins and Metabolic Diseases has been conducted with compounds not developed by Advantx Pharmaceuticals Inc. Our therapeutic candidates for Metabolic Diseases are the first truly selective, pharmaceutical-grade compounds in development targeting the Sigma receptors with clean molecules and unambiguous activity, far superior in potency, selectivity, safety, and efficacy to all others tested to date.


The Protective Role of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Protein Sigma-1 Receptor in Regulating Endothelial Inflammation and Permeability Associated with Acute Lung Injury

By Zahra Mahamed, Mohammad Shadab, Rauf Ahmad Najar, Michelle Warren Millar, Jashandeep Bal, Traci Pressley, and Fabeha Fazal Excerpt from the article published in Cells. 2024; 13(1):5. 19 December 2023, DOI: Editor’s Highlights Abstract Earlier studies from our lab identified endoplasmic reticulum (ER) chaperone BiP/GRP78, an important component of MAM, to be a novel determinant […]

Genetic and Pharmacological Blockade of Sigma-1 Receptors Attenuates Inflammation-Associated Hypersensitivity during Acute Colitis in CD1 Mice

By Sergio López-Estévez, Mònica Aguilera, Georgia Gris, Beatriz de la Puente, Alicia Carceller, and Vicente Martínez Excerpt from the article published in Biomedicines. 12 October 2023; 11(10):2758. DOI: Editor’s Highlights Abstract Sigma-1 receptors (σ1Rs) are implicated in nociception, including pain sensitization, and inflammation. We assessed the role of σ1Rs on acute colitis-associated hypersensitivity using […]

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: 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 […]

The Sigma-1 Receptor Is a Novel Target for Improving Cold Preservation in Rodent Kidney Transplants

By Adam Hosszu, Akos R. Toth, Tamas Lakat, Ganna Stepanova, Zsuzsanna Antal, Laszlo J. Wagner, Attila J. Szabo, and Andrea Fekete Excerpt from the article published in International Journal of Molecular Sciences. 19 July 2023; 24(14):11630. Editor’s highlights Abstract Kidney transplantation is the preferred treatment for patients with end-stage kidney disease. Maintaining organ viability […]

Evaluation of Some Safety Parameters of Dual Histamine H3 and Sigma-2 Receptor Ligands with Anti-Obesity Potential

By Kamil Mika, Małgorzata Szafarz, Marek Bednarski, Agata Siwek, Katarzyna Szczepańska, Katarzyna Kieć-Kononowicz, and Magdalena Kotańska Excerpt from the article published in the International Journal of Molecular Sciences 24, 19 April 2023, no. 8: 7499. DOI: Editor’s Highlights Abstract Many studies have shown the high efficacy of histamine H3 receptor ligands in preventing weight gain. In addition […]

Early Alterations of RNA Binding Protein (RBP) Homeostasis and ER Stress-Mediated Autophagy Contributes to Progressive Retinal Degeneration in the rd10 Mouse Model of Retinitis Pigmentosa (RP)

By Alfred Yamoah, Priyanka Tripathi, Haihong Guo, Leonie Scheve, Peter Walter, Sandra Johnen, Frank Müller, Joachim Weis, and Anand Goswami Excerpt from the article published in Cells. 6 April 2023; 12(7):1094. DOI: Editor’s Highlights Abstract The retinal degeneration 10 (rd10) mouse model is widely used to study retinitis pigmentosa (RP) pathomechanisms. It offers a […]

Sigmar1 ablation leads to lung pathological changes associated with pulmonary fibrosis, inflammation, and altered surfactant proteins levels

By Remex Naznin Sultana, Abdullah Chowdhury S., Aishwarya Richa, Nitu Sadia S., Traylor James, Hartman Brandon, King Judy, Bhuiyan Mohammad Alfrad Nobel, Kevil Christopher G., Orr A. Wayne, and Bhuiyan Md. Shenuarin Excerpt from the article published in Frontiers in Physiology, volume 14, 27 March 2023Sec. Respiratory Physiology and Pathophysiology, ISSN 1664-042X, DOI: 10.3389/fphys.2023.1118770 Editor’s […]

Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases

By Francisco Javier Munguia-Galaviz, Alejandra Guillermina Miranda-Diaz, Miguel Alejandro Cardenas-Sosa, and Raquel Echavarria Excerpt from the article published in the International Journal of Molecular Sciences. 19 January 2023; 24(3):1997. DOI: Editor’s Hihghlights Abstract Cardiovascular and renal diseases are among the leading causes of death worldwide, and regardless of current efforts, there is a demanding […]

Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas

By Nirmal Verma, Gopal Viswanathan Velmurugan, Edric Winford, Han Coburn, Deepak Kotiya, Noah Leibold, Laura Radulescu, Sanda Despa, Kuey C. Chen, Linda J. Van Eldik, Peter T. Nelson, Donna M. Wilcock, Gregory A. Jicha, Ann M. Stowe, Larry B. Goldstein, David K. Powel, Jeffrey H. Walton, Manuel F. Navedo, Matthew A. Nystoriak, Andrew J. Murray, […]

Sigma-1 Receptor Activation Improves Oligodendrogenesis and Promotes White-Matter Integrity after Stroke in Mice with Diabetic Mellitus

By Wenjing Song, Yang Yao, Heling Zhang, Xin Hao, Liping Zhou, Zhixiao Song, Tiantian Wei, Tianyan Chi, Peng Liu, Xuefei Ji, and Libo Zou Excerpt from the article published in Molecules 2023, 28(1), 390; 2 January 2023; DOI: Editor’s Highlights Abstract Diabetes mellitus (DM) is a major risk factor for stroke and exacerbates white-matter damage in […]

Sigma-1 Receptor as a Protective Factor for Diabetes-Associated Cognitive Dysfunction via Regulating Astrocytic Endoplasmic Reticulum-Mitochondrion Contact and Endoplasmic Reticulum Stress

By Mengyu Du, Tao Jiang, Shuxuan He Bo Cheng, Xin Zhang, Liya Li, Lan Yang, Wei Gao, Yansong Li, and Qiang Wang Excerpt from the article published in Cells 2023, 12(1), 197; 3 January 2023, DOI: Editor’s Highlights Abstract The prevalence of diabetes-associated cognitive dysfunction (DACD) has increased to 13.5%. Dementia, as the most severe DACD, […]

Effects of sub-chronic, in vivo administration of sigma-1 receptor ligands on platelet and aortic arachidonate cascade in streptozotocin-induced diabetic rats

By Sándor Váczi, Lilla Barna, Krisztián Laczi, Ferenc Tömösi, Gábor Rákhely, Botond Penke, Lívia Fülöp, Ferenc Bogár, Tamás Janáky, Mária A. Deli, and Zsófia Mezei Excerpt from the article published in Plos One on November 17, 2022, DOI: Editor’s Highlights Abstract Background: Diabetes mellitus is a chronic metabolic disorder which induces endothelial dysfunction and […]

Differential Responses to Sigma-1 or Sigma-2 Receptor Ablation in Adiposity, Fat Oxidation, and Sexual Dimorphism

By Jing Li, Elisa Félix-Soriano, Katherine R. Wright, Hongtao Shen, Lisa A. Baer, Kristin I. Stanford, and Lian-Wang Guo Excerpt from the article published in International Journal of Molecular Sciences 23, no. 18: 10846. 16 September 2022, DOI: Editor’s Highlights Obesity predisposes patients to comorbidities, including type 2 diabetes and cardiovascular disease, that significantly increase […]

GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization, mitochondria-targeting and -activating properties of human salivary histatin 1

By Dandan Ma, Wei Sun, Cuicui Fu, Kamran Nazmi, Enno C. I. Veerman, Richard T. Jaspers, Jan G. M. Bolscher, Floris J. Bikker, and Gang Wu Excerpt from the article published in International Journal of Oral Science volume 14, Article number: 42 (2022), 15 August 2022, DOI: Editor’s Highlights The histatin (Hst) peptide family […]

Roles of Transmembrane Protein 97 (TMEM97) in Adipose Tissue and Skeletal Muscle

By Masafumi Tenta, Jun Eguchi, and Jun Wada Excerpt from the article published in Acta Medica Okayama, 2022 Jun; 76 (3):235-245. DOI: 10.18926/AMO/63717 Editor’s Highlights Sarcopenic obesity, the combination of sarcopenia and obesity, is defined as reduced skeletal muscle mass and muscle strength in parallel with increased adiposity. Adipose tissue is the major site for the […]

Sigma-1 Receptor in Retina: Neuroprotective Effects and Potential Mechanisms

By Zifen Xu, Yushuang Lei, Huan Qin, Shiyao Zhang, Ping Li, and Kai Yao Excerpt from the article published in International Journal of Molecular Sciences 23, no. 14: 7572. Published: 8 July 2022, DOI: Editor’s Highlights The sigma-1 receptor is widely expressed in several organs, such as endocrine, immune, and reproductive tissues, the liver, kidney, […]

Astrocytes: the neglected stars in the central nervous system and drug addiction

By Wenjun Chen, Shiqiu Meng, Ying Han, and Jie Shi Excerpt from the article published in Medical Review, vol. , no. , 2022. Published online: June 29, 2022 DOI: Editor’s Highlights The star-shaped astrocyte, one dominant type of glia, has been implicated in myriad biological processes of the central nervous system (CNS) by interacting […]

KSK-74: Dual Histamine H3 and Sigma-2 Receptor Ligand with Anti-Obesity Potential

By Kamil Mika, Małgorzata Szafarz, Monika Zadrożna, Barbara Nowak, Marek Bednarski, Katarzyna Szczepańska, Krzysztof Pociecha, Monika Kubacka, Noemi Nicosia, Izabela Juda, Katarzyna Kieć-Kononowicz, and Magdalena Kotańska Excerpt from the article published in International Journal of Molecular Sciences 2022 23, no. 13: 7011. Published: 24 June 2022. DOI: Editor’s Highlights Ligands for H3/sigma-2 receptors promote the […]

The Link Between Energy-Related Sensations and Metabolism: Implications for Treating Fatigue

By Marco Filippi, Rainer Krähenmann, and Patrick Fissler Excerpt from the article published in Frontiers in Psychology, volume 13, 21 June 2022, DOI: Editor’s Highlights Physical exercise has been shown to improve energy-related sensations such as energetic arousal, calmness, burnout, emotional exhaustion, fatigue, and vigor. Evidence reveals a robust link between fatigue and different components […]

Molecular function of Sigma-1 receptor in obesity-induced metabolic dysfunction

By Chowdhury S. Abdullah, Shafiul Alam, Richa Aishwarya, Jonette M. Green, A. Wayne Orr, Matthew D. Woolard, Aimee E. Vozelinek, Norman R. Harris, Randa S. Eshaq, Christopher G. Kevil, and Shenuarin Bhuiyan Introduction to the article published in Journal of Molecular and Cellular Cardiology, 046| VOLUME 112, P149, NOVEMBER 01, 2017, DOI: Editor’s Highlights Sigma-1 receptor (Sigmar1) […]

Mitochondria Fusion upon SERCA Inhibition Prevents Activation of the NLRP3 Inflammasome in Human Monocytes

By Ana Catarina Pereira, Nuno Madeira, Sofia Morais, António Macedo, Maria Teresa Cruz, and Cláudia M. F. Pereira Excerpt from the article published in Cells 11, no. 3: 433, 27 January 2022, DOI: Editor’s Highlights Activation of the the Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome has been implicated in a wide range of […]

Calcium Signaling Mediates Cell Death and Crosstalk with Autophagy in Kidney Disease

By Bo Ning, Chuanzhi Guo, Anqi Kong, Kongdong Li, Yimin Xie, Haifeng Shi, and Jie Gu Excerpt from the article published in Cells, 10, 3204, 17 November 2021, DOI: Editor’s Highlights The kidney is an indispensable organ for maintaining body Ca2+ homeostasis; the Ca2+ signaling system in kidney cells regulates cellular processes and decides cell fate, including […]

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: 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 […]

Sigmar1’s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology

By Aishwarya Richa, Abdullah Chowdhury S., Morshed Mahboob, Remex Naznin Sultana, and Bhuiyan Md. Shenuarin Excerpt from the article published in Frontiers in Physiology, volume 12, 2021. DOI: Editor’s Highlights Sigma-1 receptor is a multifunctional, ubiquitously expressed chaperone protein encoded by the SIGMAR1 gene. Alterations in Sigmar1’s subcellular localization, expression, and signaling have been […]

Sigmar1 in lipid metabolism

By Shenuarin Bhuiyan A study funded by the National Institute of Health (NIH). 2021 Editor’s Highlights The molecular function of Sigma-1 receptor (Sigmar1) proteins in metabolism is associated with lipid-containing micro-domains suggesting a potential role in the pathophysiology of metabolic diseases. This study will investigate a novel function for Sigmar1 in regulating lipid metabolism in […]

Sigma 1 Receptor is Overexpressed in Hepatocellular Adenoma: Involvement of ERα and HNF1α

By Laure Villemain, Sylvie Prigent, Aurélie Abou-Lovergne, Laura Pelletier, Magali Chiral, Marco Pontoglio, Fabienne Foufelle, Stefano Caruso, Raphael Pineau, Sandra Rebouissou, Eric Chevet, Jessica Zucman-Rossi, and Laurent Combettes Excerpt from the article published in Cancers (Special Issue Therapeutic Targeting of the Unfolded Protein Response in Cancer) 2020; 12(8):2213. Editor’s Highlights Hepatocellular adenomas (HCAs) are rare […]

Sigma-1 receptor ablation impedes adipocyte-like differentiation of mouse embryonic fibroblasts

By Huan Yang, Hongtao Shen, Jing Li, Kristin I. Stanford, and Lian-Wang Guo Excerpt from the article published in Cell Signal. 2020 Nov;75:109732. DOI: 10.1016/j.cellsig.2020.109732. Epub 2020 Aug 2. PMID: 32750415; PMCID: PMC7530065. Editor’s Highlights Abstract The sigma-1 receptor (Sig1R) is a unique ligand-operated endoplasmic reticulum (ER) protein without any mammalian homolog. It has long […]

Lipid metabolic pathways converge in motor neuron degenerative diseases

By Olivia J. Rickman, Emma L. Baple and Andrew H. Crosby Excerpt from the article published in Brain, Volume 143, Issue 4, April 2020, Pages 1073–1087, Editor’s Highlights Genetic, molecular, cell and animal studies have identified dysfunctional lipid metabolic outcomes as a common theme in Motor neuron diseases (MNDs)-associated molecules. Aberrant lipid metabolism is also […]

The sigma-1 receptor as key common factor in cocaine and food-seeking behaviors

By David Aguinaga, Mireia Casanovas, Rafael Rivas-Santisteban, Irene Reyes-Resina, Gemma Navarro, and Rafael Franco Excerpt from the article published in Journal of Molecular Endocrinology, 63(4), R81-R92, November 2019, DOI: Editor’s Highlights Food-seeking behavior involve peripheral and central players, ghrelin being one of the most relevant.  Ghrelin is a peptide hormone that controls food intake and energy […]

Alpha2delta-1 in SF1+ Neurons of the Ventromedial Hypothalamus Is an Essential Regulator of Glucose and Lipid Homeostasis

By Jennifer A. Felsted, Cheng-Hao Chien, Dongqing Wang, Micaella Panessiti, Dominique Ameroso, Andrew Greenberg, Guoping Feng, Dong Kong, and Maribel Rios Excerpt from the article published in Cell Reports, volume 21, issue 10, P2737-2747, December 2017, DOI: Editor’s Highlights Alpha2delta-1 (α2δ-1) plays a chief role in energy and glucose balance control acting downstream of brain-derived neurotrophic […]