THIQ is the first selective agonist of the melanocortin-4 receptor (MC4R), with high affinity and potency for hMC4R (IC50=1.2 nM, EC50=2.1 nM) and rMC4R (IC50=0.6 nM, EC50=2.9 nM). THIQ maintains low potency at MC1R, MC3R and MC5R. THIQ plays a role in eliciting erectile activity in rodents. THIQ acts as a pharmacoperone of the MC4R rescuing the cell surface expression and signaling of some intracellularly retained MC4R mutants .
The melanocortin receptors are a family of seven-transmembrane G-protein-coupled receptors. The melanocortin subtype-4 receptor (MC4R) is expressed in various regions of the brain, and playing an important role in feeding behavior. THIQ is a potent and selective agonist of MC4R with high affinity and potency for hMC4R (IC50 = 1.2 nM, EC50 = 2.1 nM) and rMC4R (IC50 = 0.6 nM, EC50 = 2.9 nM). THIQ maintains low potency at MC1R, MC3R and MC5R[3]. THIQ (10 μM; 24 h) decreased the signal intensity of WT MC4R by ~50% whereas increased that of three mutants (N62S, C84R, and C271Y) in HEK293 cells[4]. In sexually mature male Sprague Dawley rats, THIQ (0.3-10 mg/kg; i.v.) dose-dependently increased erections with an ED50 of 0.87 mg/kg. THIQ (20 mg/kg; p.o.) also produced statistically significant increases in erectile responses with a mean increase of 31 ± 4%[3].
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