EAAT Modulator

Nε-(Carboxyethyl) lysine is an advanced glycation end product (AGE). Nε-(Carboxyethyl) lysine induces cross-linking between proteins, thereby affecting protein structure and function and causing protein denaturation. Nε-(Carboxyethyl) lysine binds to the RAGE receptor, affects cell signal transduction, and regulates processes such as inflammatory responses, cell proliferation, and apoptosis. Nε-(Carboxyethyl) lysine affects glutamate transporters, reduces glutamate uptake and S100β protein secretion, influences neurotransmission in the nervous system, and exhibits diabetes-related neurotoxicity.

(R)-AS-1 is a selective positive allosteric modulator of the excitatory amino acid transporter 2 (EAAT2), with an EC₅₀ of 11 nM. (R)-AS-1 (at doses of 60 and 90 mg/kg) increases spontaneous locomotor activity in mice. Additionally, it demonstrates anticonvulsant activity in mouse models of seizures induced by maximal electroshock (MES), pentylenetetrazole (PTZ), or electrical stimuli (32 or 44 mA), with ED₅₀s of 66.3, 36.3, 15.6, and 41.6 mg/kg, respectively. (R)-AS-1 can be used in neurological disease research.

DA-023 (Compound 4) is a selective positive allosteric modulator (PAM) of EAAT2 with an EC₅₀ value of 1 nM.

EAAT2 activator 2 (Compound 4(SF-2)) is a brain-penetrant excitatory amino acid transporter 2 (EAAT2) modulator (K_i=28.7 nM). EAAT2 activator 2 enhances EAAT2-mediated glutamate uptake, improving synaptic glutamate clearance. EAAT2 activator 2 is promising for research of neurodegenerative diseases (e.g., ALS, Alzheimer’s disease) .