Discovery of (<i>R</i>)-<i>N</i>-Benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [<b>(<i>R</i>)-AS-1</b>], a Novel Orally Bioavailable EAAT2 Modulator with Drug-like Properties and Potent Antiseizure Activity <i>In Vivo</i>
Michał Abram, Marcin Jakubiec, Katelyn Reeb, Mary Hongying Cheng, Robin Gedschold, Anna Rapacz, Szczepan Mogilski, Katarzyna Socała, Dorota Nieoczym, Małgorzata Szafarz, Gniewomir Latacz, Bartłomiej Szulczyk, Justyna Kalinowska‐Tłuścik, Kinga Gaweł, Camila V. Esguerra, Elżbieta Wyska, Christa E. Müller, İvet Bahar, Andréia C. K. Fontana, Piotr Właź, Rafał M. Kamiński, Krzysztof Kamiński
Abstract
] may be considered as the first-in-class small-molecule PAM of EAAT2 with potential for further preclinical and clinical development in epilepsy and possibly other CNS disorders.
Topics & Concepts
ChemistryPharmacologyPentylenetetrazolIn vivoAllosteric modulatorAllosteric regulationADMEPharmacokineticsIn vitroDrugEpilepsyBiochemistryAnticonvulsantReceptorBiologyNeuroscienceBiotechnologyNeuroscience and Neuropharmacology ResearchIon channel regulation and functionReceptor Mechanisms and Signaling