Universität zu Köln

Walpurgis, Katja, Thomas, Andreas ORCID: 0000-0003-1199-0743, Vogel, Matthias, Reichel, Christian, Geyer, Hans, Schaenzer, Wilhelm and Thevis, Mario (2016). Testing for the erythropoiesis-stimulating agent Sotatercept/ACE-011 (ActRIIA-Fc) in serum by means of Western blotting and LC-HRMS. Drug Test. Anal., 8 (11-12). S. 1152 - 1162. HOBOKEN: WILEY-BLACKWELL. ISSN 1942-7611

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Abstract

Sotatercept (formerly ACE-011) is a glycosylated, dimeric fusion protein composed of the extracellular domain of the human activin receptor type IIA (ActRIIA) and the Fc region of human IgG1. The protein-based drug candidate acts as a ligand trap which competitively binds to activin A and other members of the transforming growth factor beta superfamily, thus blocking signalling through ActRIIA. Since the inhibition of activin A was found to significantly increase bone formation and quality, Sotatercept was originally developed for the treatment of diseases involving bone loss. But as the protein therapeutic also stimulates erythropoiesis by a mechanism independent of the EPO receptor, it has been evaluated for the treatment of anaemia in rare blood diseases such as beta thalassemia. Due to its positive effects on erythropoiesis and bone formation, Sotatercept may also be misused as performance-enhancing agent in sports. Within this study, two complementary detection assays for Sotatercept and related ActRIIA-Fc fusion proteins in serum samples were developed. While the first assay combines affinity purification and Western blotting to generically detect ActRIIA-Fc fusion proteins irrespective of their amino acid sequence, the liquid chromatography-high resolution mass spectrometry (LC-HRMS) method is highly specific for proteolytic peptides originating from the receptor and Fc domain of Sotatercept. Both approaches can readily be modified to include other pharmaceutical proteins such as therapeutic antibodies, and serve as proof-of-concept for the capability of the approach to detect TGF-beta inhibitors and Fc fusion proteins in doping control serum samples. Copyright (C) 2016 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Walpurgis, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Andreas UNSPECIFIED orcid.org/0000-0003-1199-0743 UNSPECIFIED Vogel, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Reichel, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Geyer, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-256104
DOI:	10.1002/dta.2093
Journal or Publication Title:	Drug Test. Anal.
Volume:	8
Number:	11-12
Page Range:	S. 1152 - 1162
Date:	2016
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1942-7611
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LIGAND TRAP; POSTMENOPAUSAL WOMEN; MASS-SPECTROMETRY; RECEPTOR; SPORTS; ACE-011 Multiple languages Biochemical Research Methods; Chemistry, Analytical; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25610