| Description |
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[1][2].
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| Related Catalog |
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| In Vitro |
THIQ maintains low potency at human MC1R, MC3R and MC5R with IC50s of 2067, 761, 326 nM and EC50s of 2850, 2487, 737 nM, resepectively. THIQ maintains low potency at rat MC3R and MC5R with IC50s 1883 and 1575 nM, and EC50s of 1325 and >3000 nM, respectively[1]. THIQ (10 μM; 24 hours) decreases the signal intensity of WT MC4R by approximately 50% whereas increases that of three mutants (N62S, C84R, and C271Y) in HEK293 cells[2].
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| In Vivo |
THIQ (0.3-10 mg/kg; i.v.) dose-dependently increases erections (ED50=0.87 mg/kg) in sexually mature male Sprague Dawley rats. The maximal increase in the number of erections (60%) is detected at 5 mg/kg but was not significantly different from that produced by 1 mg/kg. THIQ (20 mg/kg; p.o.) also produces statistically significant increases in erectile responses with a mean increase of 31±4%[1]. THIQ treatment shows the t1/2 is 0.6 hours in Sprague-Dawley rats (1 mg/kg, i.v. and 10 mg/kg, p.o.)[1].
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| References |
[1]. Sebhat IK, et al. Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)- 2-[4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist. J Med Chem. 2002 Oct 10;45(21):4589-93. [2]. Huang H, et al. A small molecule agonist THIQ as a novel pharmacoperone for intracellularly retainedmelanocortin-4 receptor mutants. Int J Biol Sci. 2014 Jul 20;10(8):817-24.
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