Drug Discovery 2019 - Looking back to the future
Poster
74

Improving Valvulopathy Prediction by Qualifying 5-HT2B Functional Assay Technologies

Authors

T Jolas1; A Baron1; A Otto-Bruc1; F Redoules1; B Fouchaq1; S Davies1
1 Eurofins Discovery, France

Abstract

Valvulopathy is one of the most dramatic side effects appearing upon chronic use of some 5-HT2B agonists. Stimulation of Valvular Interstitial Cells with some 5HT2B agonists induces an abnormal proliferation of those cells while other agonists do not produce such effect. A recent paper from Papoian T et al. (Toxicol Pathol 2017; 45:381-388), presented at the 2018 SPS meeting, suggested that monitoring stimulation of mitogen activated protein kinase (MAPK) pathway was a better predictor of valvulopathy occurrence than the other three classical readouts (IP accumulation, calcium release, and beta-arrestin translocation). Eurofins Discovery set up an assay that follows MAPK activation upon 5-HT2B receptor stimulation using the same cell line in which IP accumulation is already monitored. We compared the data obtained with the two readouts for various valvulopathogens or not. Results are presented here.

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