THIQ

THIQ is a melanocortin 4 receptor (MC4R) agonist that is selective over MC1R, MC3R, and MC5R human receptors expressed in CHO cells (IC50s = 1.2, 2,067, 761, and 326 nM, respectively). It selectively increases cAMP accumulation in CHO cells expressing human MC4R over MC1R, MC3R, and MC5R (EC50s = 2.1, 2,850, 2,487, and 737 nM, respectively). THIQ also activates mutant MCR4s, which have been linked to obesity, in HeLa cells expressing the mutant receptors (EC50s = 0.23, 2.60, 39.7, and 43.6 for Wt, R165Q, C271Y, N97D, respectively). It is also selective for rat MC4R (IC50 = 0.6 nM) over rat MC3R and MC5R (IC50s = 1,883 and 1,575 nM, respectively). In vivo, THIQ (5 mg/kg, i.v.) increases the number of penile erections by 92% in a rat ex copula model of penile erection. It also inhibits food intake after an overnight fast and decreases nocturnal feeding behavior in mice when administered at 32 nmol (i.c.v.).