Glutamate (EAAT) Transporters

ONO 2506 inhibits S100B synthesis in activated cultured astrocytes.

UCPH 101 is a selective non-substrate inhibitor of EAAT1 (IC50 values are 660, >300000 and >300000 nM for EAAT1, EAAT2 and EAAT3 respectively).

GT 949 is a selective excitatory amino acid transporter-2 (EAAT2) positive allosteric modulator with an EC50 of 0.26 nM.

WAY-213613 is a potent, selective nonsubstrate reuptake inhibitor of GLT-1/EAAT2 with IC50 of 85 nM EAAT2.

MPDC is a potent and competitive inhibitor of the Na+-dependent high-affinity glutamate transporter in forebrain synaptosomes.

GPNA hydrochloride is a well known substrate of the enzyme γ-glutamyltransferase (GGT). GPNA hydrochloride is a specific glutamine (Gln) transporter ASCT2 inhibitor.

Evans Blue is a potent inhibitor of L-glutamate uptake through the membrane-bound excitatory amino acid transporter (EAAT). This compound effectively inhibits L-glutamate and kainate receptor-mediated currents, making it valuable for research into neurophysiological processes. Additionally, due to its strong affinity for serum albumin, Evans Blue serves as a high molecular weight protein tracer and is widely used to investigate blood-brain barrier (BBB) permeability.

DL-TBOA is a potent non-transportable inhibitor of excitatory amino acid transporters (EAATs), specifically targeting EAAT1, EAAT2, and EAAT3 with IC50 values of 70 μM, 6 μM, and 6 μM, respectively. This compound effectively inhibits the uptake of [14C]glutamate in COS-1 cells expressing human EAAT1 and EAAT2, demonstrating Ki values of 42 μM and 5.7 μM, respectively. Additionally, DL-TBOA competitively blocks EAAT4 and EAAT5 with Ki values of 4.4 μM and 3.2 μM, respectively. This reagent is valuable for studying excitatory neurotransmission and related pathologies in research applications.

LDN-212320 is a potent activator of the glutamate transporter GLT-1 (EAAT2), primarily functioning at the translational level. This compound is known to mitigate nociceptive pain by enhancing astroglial GLT-1 expression in both the hippocampus and anterior cingulate cortex. LDN-212320 is valuable in research focused on pain modulation and neuroprotection, offering insights into the role of glutamate transporters in neurological conditions.

WAY-213613 hydrochloride is a potent and selective inhibitor of the human excitatory amino acid transporter 2 (EAAT2). With an IC50 value of 85 nM, it effectively modulates glutamate transport, making it a valuable tool for investigating glutamatergic signaling in the central nervous system. This compound is suitable for research applications exploring neurobiology and potential therapeutic interventions related to neurodegenerative diseases.

NA-014 is a selective positive allosteric modulator (PAM) of the excitatory amino acid transporter 2 (EAAT2), exhibiting an EC50 of 3 nM. This compound enhances the transport activity of EAAT2, which is crucial for regulating glutamate levels in the synaptic cleft. NA-014 is valuable for research into neurodegenerative diseases and synaptic dysfunction, providing insights into therapeutic strategies that target glutamate homeostasis.

UCPH-102 is a highly selective inhibitor of the excitatory amino acid transporter 1 (EAAT1), exhibiting an IC50 value of 0.43 µM. This compound demonstrates significant anti-proliferative effects on T-cell acute lymphoblastic leukemia (T-ALL) cells. Furthermore, UCPH-102's favorable blood-brain barrier permeability makes it a valuable tool for research in neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer’s disease, as well as conditions related to chronic pain and obsessive-compulsive disorder.

L-threo-3-Hydroxyaspartic acid functions as a selective inhibitor of excitatory amino acid transporters (EAATs), exhibiting inhibitory constants (Kis) of 11, 19, and 14 μM for EAAT1, EAAT2, and EAAT3, respectively, in HEK293 cell lines. This compound plays a crucial role in the study of neurotransmitter regulation and excitotoxicity, making it valuable for research related to neurological disorders and synaptic transmission. Its ability to modulate glutamate signaling contributes to understanding potential therapeutic pathways for conditions such as epilepsy and neurodegenerative diseases.

Nε-(Carboxyethyl)lysine is a known modulator of excitatory amino acid transporters (EAATs). As an advanced glycation end product (AGE), it facilitates protein cross-linking, leading to alterations in protein structure and function, ultimately resulting in protein denaturation. Nε-(Carboxyethyl)lysine interacts with RAGE receptors, influencing cell signaling pathways critical for inflammatory response, cell proliferation, and apoptosis. Additionally, it affects glutamate transporter activity, reducing glutamate uptake and S100B protein secretion, thereby impacting neurotransmission and demonstrating neurotoxic effects associated with diabetes.

EAAT2 Activator 1 is a potent activator of the excitatory amino acid transporter 2 (EAAT2), a critical protein responsible for the clearance of glutamate from synaptic clefts. This compound enhances EAAT2 protein levels in a dose-dependent manner, promoting efficient glutamate uptake. EAAT2 Activator 1 is relevant for research applications aimed at understanding glutamatergic signaling and neuroprotection in various neurological disorders.

(R)-AS-1 is a selective positive allosteric modulator of the excitatory amino acid transporter 2 (EAAT2), exhibiting an EC50 of 11 nM. This compound enhances spontaneous locomotor activity in murine models at doses of 60 and 90 mg/kg. Additionally, (R)-AS-1 demonstrates significant anticonvulsant effects in various seizure models, with ED50 values of 66.3 mg/kg for maximal electroshock, 36.3 mg/kg for pentylenetetrazole, and 41.6 mg/kg for electrical stimuli. This agent is valuable for research in neurological disorders.

SLC1A1/EAAT3-IN-1 is a selective inhibitor of the excitatory amino acid transporter 3 (EAAT3), exhibiting an IC50 of 7.2 μM for human EAAT3 while showing significantly reduced inhibition of EAAT1, 2, and 4 (IC50: ~250 μM). This compound is primarily utilized in research related to psychiatric disorders, including obsessive-compulsive disorder and schizophrenia, and can aid in the investigation of neurotransmitter dynamics and therapeutic strategies targeting EAAT3.

(±)-HIP-B is a non-competitive blocker of excitatory amino acid transporters (EAATs), demonstrating effective inhibition of glutamate uptake with an IC50 of 17-18 μM. This compound serves as a valuable lead in research focused on ischemia-induced neuronal degeneration. Its application extends to the investigation of various neurological disorders, contributing to a deeper understanding of excitotoxicity and neuronal survival mechanisms.

DL-TBOA ammonium is a selective inhibitor of excitatory amino acid transporters (EAATs), demonstrating IC50 values of 70 μM, 6 μM, and 6 μM for EAAT1, EAAT2, and EAAT3, respectively. This compound effectively inhibits the uptake of [14C]glutamate in COS-1 cells expressing human EAAT1 and EAAT2, with Ki values of 42 μM and 5.7 μM. Additionally, DL-TBOA ammonium competitively inhibits EAAT4 and EAAT5, featuring Ki values of 4.4 μM and 3.2 μM, respectively. Its distinct mechanism renders it a valuable tool for studies on excitatory neurotransmission and the role of glutamate transporters in neurological research.

(±)-threo-3-Methylglutamic acid is a potent inhibitor of excitatory amino acid transporters EAAT2 and EAAT4. It functions as an ionotropic glutamate receptor agonist and is effective in inhibiting glutamate uptake in rod outer segments. This compound is valuable for research applications focusing on glutamatergic signaling and transport mechanisms in the nervous system.

DA-023 is a selective positive allosteric modulator of the excitatory amino acid transporter 2 (EAAT2) with an EC50 value of 1 nM. This compound enhances EAAT2 activity, which is crucial for glutamate regulation in the central nervous system. DA-023 is particularly relevant for research into neurological diseases, offering potential insights into therapeutic strategies for conditions associated with glutamate dysregulation.

(±)-HIP-A is a non-competitive blocker of excitatory amino acid transporters (EAATs) that inhibits glutamate uptake with an IC50 value of 17-18 μM. This compound serves as a lead candidate for research into ischemia-induced neuronal degeneration. (±)-HIP-A is particularly valuable for studying the pathophysiology of neurological diseases and the mechanisms underlying excitotoxicity.