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 an orally active EAAT2 enhancer that crosses the blood-brain barrier. (R)-AS-1 enhances EAAT2-mediated glutamate uptake by increasing the transport rate without altering substrate affinity. (R)-AS-1 can be used for research on epilepsy.

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) .