ArticleBiochemistry2015
Structure-Based Identification of Inhibitors for the SLC13 Family of Na(+)/Dicarboxylate Cotransporters.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Discovery and Characterization of a Nonacidic Small-Molecule Inhibitor of the Sodium-Coupled Dicarboxylate Transporter NaCT.Journal of medicinal chemistry · 2026Article
- SLC13A2-transported citrate remodels transcriptional regulation through protein acetylation to suppress tumor growth.Science advances · 2026Article
- Metabolic Symbiosis Between Cancer Cells and Endothelial Cells: A Key Driver of Tumor Angiogenesis.Advances in experimental medicine and biology · 2026Review
- Substrate translocation and inhibition in human dicarboxylate transporter NaDC3.Nature structural & molecular biology · 2025Article
- SLC13A2 promotes hepatocyte metabolic remodeling and liver regeneration by enhancing de novo cholesterol biosynthesis.The EMBO journal · 2025Article
- Identification of hub glutamine metabolism-associated genes and immune characteristics in pre-eclampsia.PloS one · 2024Article
- Targeting SLC transporters: small molecules as modulators and therapeutic opportunities.Trends in biochemical sciences · 2023Review
- Role of sodium dependent SLC13 transporter inhibitors in various metabolic disorders.Molecular and cellular biochemistry · 2023Review
- The pathogenesis of, and pharmacological treatment for, Canavan disease.Drug discovery today · 2022Review
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
- Article
- INDY-From Flies to Worms, Mice, Rats, Non-Human Primates, and Humans.Frontiers in aging · 2021Review
- Studies of structural determinants of substrate binding in the Creatine Transporter (CreaT, SLC6A8) using molecular models.Scientific reports · 2020Article
- Structure and Mechanism of the Divalent Anion/Na⁺ Symporter.International journal of molecular sciences · 2019Review
- Discovery of Potent Inhibitors for the Large Neutral Amino Acid Transporter 1 (LAT1) by Structure-Based Methods.International journal of molecular sciences · 2018Article
- Molecular Modeling of Drug-Transporter Interactions-An International Transporter Consortium Perspective.Clinical pharmacology and therapeutics · 2018Review
- Analysis of naturally occurring mutations in the human uptake transporter NaCT important for bone and brain development and energy metabolism.Scientific reports · 2018Article
- Chemical Modulation of the Human Oligopeptide Transporter 1, hPepT1.Molecular pharmaceutics · 2017Article
- Inhibitor Discovery for the Human GLUT1 from Homology Modeling and Virtual Screening.ACS chemical biology · 2016Article
- SLC Transporters: Structure, Function, and Drug Discovery.MedChemComm · 2016Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
In mammals, citric acid cycle intermediates play a key role in regulating various metabolic processes, such as fatty acid synthesis and glycolysis. Members of the sodium-dependent SLC13 transporter family mediate the transport of di- and tricarboxylates into cells. SLC13 family members have been implicated in lifespan extension and resistance to high-fat diets; thus, they are emerging drug targets for aging and metabolic disorders. We previously characterized key structural determinants of substrate and cation binding for the human NaDC3/SLC13A3 transporter using a homology model. Here, we combine computational modeling and virtual screening with functional and biochemical testing, to identify nine previously unknown inhibitors for multiple members of the SLC13 family from human and mouse. Our results reveal previously unknown substrate selectivity determinants for the SLC13 family, including key residues that mediate ligand binding and transport, as well as promiscuous and specific SLC13 small molecule ligands. The newly discovered ligands can serve as chemical tools for further characterization of the SLC13 family or as lead molecules for the future development of potent inhibitors for the treatment of metabolic diseases and aging. Our results improve our understanding of the structural components that are important for substrate specificity in this physiologically important family as well as in other structurally related transport systems.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.