Description
UCPH-101 is a noncompetitive inhibitor of excitatory amino acid transporter 1 (EAAT1), which takes up extracellular glutamate in the central nervous system. UCPH-1 is selective for EAAT1 over EAAT2 and EAAT3 with IC
50 values of 0.66, >300, and >300 μM, respectively, in a radioligand uptake assay using HEK293 cells transfected with the human transporter. It selectively inhibits anion currents in tsA201 cells expressing human EAAT1 (K
d = 0.34 μM) over rat EAAT4 and mouse EAAT5 at concentrations up to 10 μM. UCPH-101 is orally bioavailable in rats at a dose of 10 mg/kg but does not cross the blood-brain barrier.
References
[1] ANDERS A. JENSEN*. Discovery of the First Selective Inhibitor of Excitatory Amino Acid Transporter Subtype 1[J]. Journal of Medicinal Chemistry, 2009, 52 4: 912-915. DOI:
10.1021/jm8013458[2] METTE N. ERICHSEN. Structure−Activity Relationship Study of First Selective Inhibitor of Excitatory Amino Acid Transporter Subtype 1: 2-Amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101)[J]. Journal of Medicinal Chemistry, 2010, 53 19: 7180-7191. DOI:
10.1021/jm1009154[3] CRISTINA CORBETTA. Altered function of the glutamate–aspartate transporter GLAST, a potential therapeutic target in glioblastoma[J]. International Journal of Cancer, 2018, 144 10: 2539-2554. DOI:
10.1002/ijc.31985
