ArticleACS chemical neuroscience2019
Identification of a Novel Allosteric Modulator of the Human Dopamine Transporter.
Article in ACS chemical neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Unlocking the Potential of High-Quality Dopamine Transporter Pharmacological Data: Advancing Robust Machine Learning-Based QSAR Modeling.Advances in neurobiology · 2025Review
- Novel Ways of Targeting the Dopamine Transporter.Advances in neurobiology · 2025Review
- Pharmacological Mechanisms of SLC6 Neurotransmitter Transporter Inhibition.Advances in neurobiology · 2025Review
- Cryo-EM structure of the dopamine transporter with a novel atypical non-competitive inhibitor bound to the orthosteric site.Journal of neurochemistry · 2024Article
- Article
- Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments.Current research in physiology · 2024Article
- Targeting SLC transporters: small molecules as modulators and therapeutic opportunities.Trends in biochemical sciences · 2023Review
- Overview of the structure and function of the dopamine transporter and its protein interactions.Frontiers in physiology · 2023Review
- Discovery and Development of Monoamine Transporter Ligands.Advances in neurobiology · 2023Review
- Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer's disease.Frontiers in cellular neuroscience · 2023Review
- Structural insights into GABA transport inhibition using an engineered neurotransmitter transporter.The EMBO journal · 2022Article
- Molecular characterization of the serotonergic transporter from the cestode Echinococcus granulosus: pharmacology and potential role in the nervous system.Parasitology research · 2022Article
- Allosteric Modulator KM822 Attenuates Behavioral Actions of Amphetamine inMolecular pharmacology · 2022Article
- The dopamine transporter gene SLC6A3: multidisease risks.Molecular psychiatry · 2022Article
- Illumination of serotonin transporter mechanism and role of the allosteric site.Science advances · 2021Article
- The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter.Nature communications · 2021Article
- Functional Characterization of the Dopaminergic Psychostimulant Sydnocarb as an Allosteric Modulator of the Human Dopamine Transporter.Biomedicines · 2021Article
- Functional characterization of N-octyl 4-methylamphetamine variants and related bivalent compounds at the dopamine and serotonin transporters using CaToxicology and applied pharmacology · 2021Article
- Allosteric Modulation of Neurotransmitter Transporters as a Therapeutic Strategy.Trends in pharmacological sciences · 2020Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The dopamine transporter (DAT) serves a pivotal role in controlling dopamine (DA)-mediated neurotransmission by clearing DA from synaptic and perisynaptic spaces and controlling its action at postsynaptic DA receptors. Major drugs of abuse such as amphetamine and cocaine interact with DAT to mediate their effects by enhancing extracellular DA concentrations. We previously identified a novel allosteric site in the related human serotonin transporter that lies outside the central substrate and inhibitor binding pocket. We used the hybrid structure based (HSB) method to screen for allosteric modulator molecules that target a similar site in DAT. We identified a compound, KM822, that was found to be a selective, noncompetitive inhibitor of DAT. We confirmed the structural determinants of KM822 allosteric binding within the allosteric site by structure/function and substituted cysteine scanning accessibility biotinylation experiments. In the in vitro cell-based assay and ex vivo in both rat striatal synaptosomal and slice preparations, KM822 was found to decrease the affinity of cocaine for DAT. The in vivo effects of KM822 on cocaine were tested on psychostimulant-associated behaviors in a planarian model where KM822 specifically inhibited the locomotion elicited by DAT-interacting stimulants amphetamine and cocaine. Overall, KM822 provides a unique opportunity as a molecular probe to examine allosteric modulation of DAT function.
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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.