Last update 01 Nov 2024

TMEM219

Last update 01 Nov 2024

Basic Info

Synonyms

IGFBP-3R, Insulin-like growth factor-binding protein 3 receptor, TMEM219

+ [1]

Introduction

Cell death receptor specific for IGFBP3, may mediate caspase-8-dependent apoptosis upon ligand binding.

Drugs associated with TMEM219

Ebrasodebart

Target

TMEM219

Mechanism

TMEM219 inhibitors

Active Org.

Enthera SrlStartup

Originator Org.

Enthera SrlStartup

Active Indication

Inflammatory Bowel Diseases [+1]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with TMEM219

NL-OMON51546 / RecruitingNot Applicable

A phase 1, randomised, double-blind, placebo-controlled, single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of Ent001 in healthy subjects - Ent001 IV First in Human SAD Study in adult healthy subjects

Start Date09 Jan 2023

Sponsor / Collaborator-

100 Clinical Results associated with TMEM219

100 Translational Medicine associated with TMEM219

0 Patents (Medical) associated with TMEM219

Literatures (Medical) associated with TMEM219

25 Sep 2023·The Kurume medical journal

Chitinase 3-Like-1 Expression Is Upregulated Under Inflammatory Conditions in Human Oral Epithelial Cells.

Article

Author: Teratani, Yui

OBJECTIVEChitinase 3-like-1 (CHI3L1), also known as YKL-40, is a partially secreted glycoprotein and is involved in inflammatory disorders, including inflammatory bowel diseases. CHI3L1 is known to play a role in biological responses such as cell proliferation, tissue remodeling, and inflammation. CHI3L1 forms an immune complex (known as a Chitosome complex) with IL-13 receptor alpha 2 (IL-13 Rα2) and transmembrane protein 219 (TMEM219) to activate the MAPK/ERK and PKB/AKT signaling pathways. The objective of this study is to investigate how the expressions of CHI3L1 and a Chitosome complex in human oral cavity epithelial cells are linked with intraoral inflammatory diseases.METHODCHI3L1 and Chitosome complex mRNA expressions were analyzed using human oral squamous cancer cell lines, HSC3 and HSC4 cells. Signaling activation in HSC4 cells was analyzed by using the western blot technique. Immunohistological analysis was performed using surgical samples obtained from patients with benign oral cavity tumors and cysts.RESULTSIncreased expression of CHI3L1 was observed in both HSC3 and HSC4 cells after TNFα stimulation. The expression of Chitosome complex factors increased as CHI3L1 levels increased, resulting in the activation of a downstream signaling pathway. Among the intraoral tissues, the epithelial cells from inflammatory lesions, but not benign tumors, were found to be intensively stained with the anti-CHI3L1 antibody.CONCLUSIONIt was indicated that the formation of a Chitosome complex is induced during inflammation, leading to the activation of signaling pathways.

01 Jun 2023·BioEssays : news and reviews in molecular, cellular and developmental biology

Targeting a novel apoptotic pathway in human disease.

Article

Author: Assi, Emma ; Petrazzuolo, Adriana ; Lunati, Maria Elena ; Fiorina, Paolo ; D'Addio, Francesca ; Bruckmann, Chiara ; Marin, Virna ; Pastore, Ida ; Montefusco, Laura

Apoptotic pathways have always been regarded as a key-player in preserving tissue and organ homeostasis. Excessive activation or resistance to activation of cell death signaling may indeed be responsible for several mechanisms of disease, including malignancy and chronic degenerative diseases. Therefore, targeting apoptotic factors gained more and more attention in the scientific community and novel strategies emerged aimed at selectively blocking or stimulating cell death signaling. This is also the case for the TMEM219 death receptor, which is activated by a circulating ligand, the Insulin-like growth factor binding protein 3 (IGFBP3) and induces a caspase-8-dependent apoptosis of the target cells. Interestingly, stimulation of the IGFBP3/TMEM219 axis exerts an anti-proliferative effect, while blockade of the TMEM219 deleterious signal protects TMEM219-expressing cells of the endocrine pancreas, lung, and intestine from damage and death. Here, we summarize the most updated reports on the role of the IGFBP3/TMEM219 apoptotic axis in disease conditions, including intestinal disorders and diabetes, and we describe the advancements in designing and testing novel TMEM219-based targeting approaches in emerging potential clinical applications.

01 Jan 2022·Advanced Biomedical Research

Expression of Recombinant Insulin-Like Growth Factor-Binding Protein-3 Receptor in Mammalian Cell Line and Prokaryotic (Escherichia coli) Expression Systems

Article

Author: Naseri, Nima ; Mirian, Mina ; Mofid, Mohammad Reza

Background:Insulin-like growth factor binding protein-3 receptor (IGFBP-3R) (Transmembrane protein 219 [TMEM219]) binds explicitly to IGFBP-3 and exerts its apoptotic and autophagy signalling pathway. Constructing a Henrietta Lacks (HeLa) h6-TMEM219 cell characterize the therapeutic potent of TMEM219 that could interrupt the IGFBP-3/TMEM219 pathway, in cancer treatment and destructive cell illnesses such as diabetes and Alzheimer's.Materials and Methods:First, to develop stable overexpressed HeLa h6-TMEM219 cells, and Escherichia coli BL21 (DE3) with high IGFBP-3R expression, the purchased pcDNA3.1-h6-TMEM219 plasmid was transformed and integrated using CaCl2 and chemical transfection reagents, respectively. The pcDNA3.1-h6-TMEM219 transfection and protein expression was evaluated by the polymerase chain reaction (PCR), western blotting, and flow cytometry. Following the induction of h6-TMEM219 expression, a protein was purified using Ni-NTA chromatography and evaluated by the sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE).Results:The 606 base pairs sequence in PCR outcomes confirmed successful pcDNA3.1-h6-TMEM219 transformation in E. Coli BL21 and integration into the HeLa genome. The analysis of protein samples from induced E. Coli BL21 and purified protein demonstrate a band of approximately 22 kDa on SDS-PAGE. Moreover, besides western blot analysis, flow cytometry findings illustrate approximately 84% of transfected HeLa cells (HeLa h6-TMEM219) overexpressed h6-TMEM219 on their surface.Conclusion:We designed a new experiment in the h6-TMEM219 expression procedure in both eukaryotic and prokaryotic hosts. All of our results confirm appropriate transformation and transfection and importantly, approve h6-TMEM 219 membrane expression. Finally, the HeLa h6-TMEM219 cells and the newly purified h6-TMEM219 leverage new studies for molecular diagnostic studies and characterize the therapeutic agents against IGFBP-3/TMEM219 signalling pathway in devastating illnesses in vitro and in vivo.

News (Medical) associated with TMEM219

07 Mar 2023

·www.biospace.com

Enthera Pharmaceuticals Initiates Phase 1 Clinical Trial with Lead Candidate Ent001

Phase 1 study in healthy volunteers lays groundwork for Ent001 evaluation in patients with inflammatory bowel disease and type 1 diabetes MILAN--(BUSINESS WIRE)-- Enthera Pharmaceuticals (“Enthera”), a biotech company developing first-in-class biologics for selected autoimmune conditions, today announces the start of a Phase 1 first-in-human (FIH) clinical trial with its lead candidate Ent001. Ent001 is a monoclonal antibody (mAb) targeting the IGFBP3/TMEM219 pathway, which plays a critical role in both inflammatory bowel disease (IBD) and type 1 diabetes (T1D). Elevated levels of IGFBP3 bind to the TMEM219 receptor, causing apoptosis of both colonic stem cells in the gut and insulin-producing beta cells in the pancreas. Ent001 is designed to bind to TMEM219 and prevent cell death and the inflammation underlying these disease states. The trial in healthy volunteers will evaluate Ent001’s safety and tolerability and establish optimal dose levels for subsequent trials in patients with IBD and T1D, the target indications for the next stage of Ent001’s clinical development. “The initiation of this trial is a major development milestone for Ent001 and transitions Enthera into a clinical stage company. The data we gather from this study will be instrumental to optimize the development of our lead candidate and enable future development in IBD and T1D,” said Aled Paton Williams, CEO of Enthera. The Phase 1 trial will evaluate Ent001 in up to 30 healthy adult volunteers in a randomised, double-blind, placebo-controlled single ascending dose (SAD) study in the Netherlands. In addition to safety, the trial will assess Ent001’s pharmacokinetics, pharmacodynamics, and immunogenicity. “This trial builds on our robust preclinical data that revealed a strong safety pro demonstrated noteworthy results with Ent001’s unique mode of action in well-established animal disease models. We look forward to applying our unique understanding of the recently discovered IGFBP3/TMEM219 axis to establish Ent001’s potential as a first-in-class therapeutic with the ability to halt and reverse disease progression in IBD and T1D,” said Filippo Canducci, Chief Medical Officer of Enthera. About Enthera Pharmaceuticals Enthera Srl is a biotech company developing first-in-class biologics to transform the treatment paradigm for specific autoimmune conditions by preserving and re-establishing cell and organ function. The Company’s primary target indications are inflammatory bowel disease (IBD) and type 1 diabetes (T1D). Enthera’s pioneering approach capitalizes on the key discovery of the IGFBP3/TMEM219 pathway, which is involved in stem cell and beta cell apoptosis in the gut and pancreas, respectively. Enthera is a private company headquartered in Milan, Italy, and founded in 2016 by Prof. Paolo Fiorina and Dr. Francesca D’Addio at BiovelocITA, Italy’s first biotech accelerator. The Company is backed by Sofinnova Partners, AbbVie INC, JDRF T1D Fund, Roche Finance LTD and a number of private investors. Enthera’s discovery engine and assets are protected by a broad portfolio of patents. For further information: View source version on businesswire.com: Contacts Enthera Pharmaceuticals Aled Williams, CEO info@entherapharmaceuticals.com Trophic Communications Valeria Fisher or Veronika Máté +49 175 8041816 or +49 160 90816161 enthera@trophic.eu Source: Enthera View this news release online at:

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