Jain A, Bozovicar K, Mehrotra V, Bratkovic T, Johnson MH, Jha I. Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders. World J Diabetes 2022; 13(6): 434-441 [PMID: 35800412 DOI: 10.4239/wjd.v13.i6.434]
Corresponding Author of This Article
Arjun Jain, MPhil, PhD, Research Scientist, ET-Traps Limited, 28 St Stephens Place, Cambridge CB3 0JE, United Kingdom. jain_arjun@yahoo.com
Research Domain of This Article
Pharmacology & Pharmacy
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Jun 15, 2022; 13(6): 434-441 Published online Jun 15, 2022. doi: 10.4239/wjd.v13.i6.434
Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders
Arjun Jain, Kristof Bozovicar, Vidhi Mehrotra, Tomaz Bratkovic, Martin H Johnson, Ira Jha
Arjun Jain, Vidhi Mehrotra, Ira Jha, ET-Traps Limited, Cambridge CB3 0JE, United Kingdom
Arjun Jain, Martin H Johnson, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, United Kingdom
Arjun Jain, Vidhi Mehrotra, Accelerate Cambridge, Judge Business School, University of Cambridge, Cambridge CB2 1AG, United Kingdom
Kristof Bozovicar, Tomaz Bratkovic, Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Slovenia 1000, Slovenia
Author contributions: Jain A and Bozovičar K contributed equally to this work; Jain A, Bozovičar K, Mehrotra V, Bratkovič T performed the experimental analyses and contributed towards writing the article and Johnson M and Jha I revised it critically for important intellectual content.
Institutional review board statement: This study was approved by ET-traps Limited.
Conflict-of-interest statement: The authors have no conflict of interest.
Data sharing statement: Data available from corresponding author, Dr. Arjun Jain at arjun@et-traps.co.uk.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Arjun Jain, MPhil, PhD, Research Scientist, ET-Traps Limited, 28 St Stephens Place, Cambridge CB3 0JE, United Kingdom. jain_arjun@yahoo.com
Received: January 27, 2022 Peer-review started: January 27, 2022 First decision: April 18, 2022 Revised: April 24, 2022 Accepted: May 28, 2022 Article in press: May 28, 2022 Published online: June 15, 2022
Abstract
BACKGROUND
Endothelin (ET)-traps are Fc-fusion proteins with a design based on the physiological receptors of ET-1. Previous work has shown that use of the selected ET-traps potently and significantly reduces different markers of diabetes pathology back to normal, non-disease levels.
AIM
To demonstrate the selected ET-traps potently and significantly bind to ET-1.
METHODS
We performed phage display experiments to test different constructs of ET-traps, and conducted bio-layer interferometry binding assays to verify that the selected ET-traps bind specifically to ET-1 and display binding affinity in the double-digit picomolar range (an average of 73.8 rM, n = 6).
RESULTS
These experiments have confirmed our choice of the final ET-traps and provided proof-of-concept for the potential use of constructs as effective biologics for diseases associated with pathologically elevated ET-1.
CONCLUSION
There is increased need for such therapeutics as they could help save millions of lives around the world.
Core Tip: This study verified the specificity of endothelin (ET)-traps, which are an Fc-based fusion protein that acts as a potential therapeutic for various cET-1 related disorders, including diabetes and chronic kidney disease. ET-traps, unlike ET receptor antagonists, do not completely block the ET system and hence have minimal side effects. ET-traps would help save millions of lives around the world.
