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Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader
Published on: May 24, 2024
Low molecular weight activated protein C inhibitors as a potential treatment for hemophilic disorders
Guillaume De Nanteuil1, Philippe Gloanec, Suzette Béguin
1Division D of Medicinal Chemistry and Division of Angiology, Institut de Recherches Servier, 11 Rue des Moulineaux, 92150 Suresnes, France. guillaume.denanteuil@fr.netgrs.com
Abstract:
The synthesis and evaluation of inhibitors of activated protein C (aPC) are reported. This serine protease is partly responsible for the degradation of factor VIIIa, involved in the regulation of bleeding in hemophilia A. Benzamidine-containing derivatives were found to be potent aPC inhibitors, some of them showing selectivity against the procoagulant protease thrombin. Moreover, compound 1 significantly restored the generation of thrombin in hemophiliac plasma.
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