Alexandra Greindl

Andreas Rybka

Andy J.G. Pötgens

Bettina Breuer

Claudia Kessler

Hans-Georg Frank

Marco Emgenbroich

Udo Haber

  We developed and tested a compound called AGEM400(HES) that consists of a novel erythropoietin mimetic
peptide (EMP) which is produced as a continuous N- to C-linked dimer and is conjugated to biodegradable hydroxyethyl
starch (HES). In various in vitro assays, AGEM400(HES) demonstrated excellent efficacy, better than the peptide alone,
and comparable to the efficacy of erythropoietin (EPO) and Aranesp (Darbepoietin alpha). The assays included survival
assays on EPO-responsive cell lines (EC50 below 1 ng/ml peptide) and clonogenic assays on human bone marrow
cells (EC50 1 to 10 ng/ml). AGEM400(HES) caused phosphorylation of STAT5 and ERK signalling proteins in UT7/EPO
cells in a similar fashion as EPO. AGEM400(HES) replaced EPO from its receptor and the in vitro activity of AGEM400
(HES) was inhibited by soluble EPO receptor. Antibodies generated in mice and rabbits against EPO did not recognize
AGEM400(HES) peptide, and vice versa. A sensitive ELISA was able to detect AGEM400(HES) at low nanogram per
ml concentrations which allows for bioanalytics of AGEM400(HES) serum levels in future in vivo studies. As a result,
AGEM400(HES) is a promising drug candidate for anemias related to renal insufficiency and/or in oncological settings. </jats:p

Crossref

The Open Hematology Journal

AGEM400(HES), a Novel Erythropoietin Mimetic Peptide Conjugated to Hydroxyethyl Starch with Excellent In Vitro Efficacy

AGEM400(HES), a Novel Erythropoietin Mimetic Peptide Conjugated to Hydroxyethyl Starch with Excellent In Vitro Efficacy

Abstract

Similar works

Full text

Available Versions

Crossref