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.
Uses
UCPH 101 is a subtype-selective inhibitor of human excitatory amino acid transporter subtype 1.
References
1) Jensen?et al.?(2009),?Discovery of the First Selective Inhibitor of Excitatory Amino Acid Transporter Subtype 1; J. Med. Chem.,?52?912
2) Erichsen?et al.?(2010),?Structure-Activity Relationship Study of the 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. Med. Chem.,?53?7180
3) Corbetta?et al.?(2019),?Altered function of the glutamate-aspartate transporter GLAST, a potential therapeutic target in glioblastoma; Int. J. Cancer,?144?2539
