Journal article
Synthesis and Structure-Activity Relationships for Glutamate Transporter Allosteric Modulators
Journal of medicinal chemistry, v 67(8), pp 6119-6143
25 Apr 2024
PMID: 38626917
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Excitatory amino acid transporters (EAATs) are essential CNS proteins that regulate glutamate levels. Excess glutamate release and alteration in EAAT expression are associated with several CNS disorders. Previously, we identified positive allosteric modulators (PAM) of EAAT2, the main CNS transporter, and have demonstrated their neuroprotective properties in vitro. Herein, we report on the structure-activity relationships (SAR) for the analogs identified from virtual screening and from our medicinal chemistry campaign. This work identified several selective EAAT2 positive allosteric modulators (PAMs) such as compounds 4 (DA-023) and 40 (NA-014) from a library of analogs inspired by GT949, an early generation compound. This series also provides nonselective EAAT PAMs, EAAT inhibitors, and inactive compounds that may be useful for elucidating the mechanism of EAAT allosteric modulation.
Metrics
1 Record Views
Details
- Title
- Synthesis and Structure-Activity Relationships for Glutamate Transporter Allosteric Modulators
- Creators
- Andreia C. K. Fontana (Corresponding Author) - Drexel UniversityAdi N. R. Poli - The Wistar InstituteJitendra Gour - The Wistar InstituteYellamelli V. V. Srikanth - The Wistar InstituteNicholas Anastasi - The Wistar InstituteDevipriya Ashok - The Wistar InstituteApeksha Khatiwada - Drexel UniversityKatelyn L. Reeb - Drexel UniversityMary Hongying Cheng - Stony Brook UniversityIvet Bahar - Stony Brook UniversityScott M. Rawls - Temple UniversityJoseph M. Salvino - The Wistar Institute
- Publication Details
- Journal of medicinal chemistry, v 67(8), pp 6119-6143
- Publisher
- ACS Publications
- Number of pages
- 25
- Grant note
- National Institute of Mental Health's Psychoactive Drug Screening Program; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) HHSN-271-2018-00023-C / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01 DA051205-03; NS111767; S10OD030245-01; P30 CA010815-53 / , National Institute on Drug Abuse; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) Bryan L. Roth MD, PhD at the University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:001204957300001
- Scopus ID
- 2-s2.0-85190732520
- Other Identifier
- 991022202111804721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
Source: SDGs in the Output
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Medicinal