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).¹ 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, and N97D, respectively).^2,3 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.⁴ It also inhibits food intake after an overnight fast and decreases nocturnal feeding behavior in mice when administered at 32 nmol (i.c.v.).⁵

WARNING This product is not for human or veterinary use.

1. Sebhat, I.K., Martin, W.J., Ye, Z., 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. 45(21), 4589-4593 (2002).

2. Farooqi, I.S., Keogh, J.M., Yeo, G.S.H., et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N. Engl. J. Med. 348(12), 1085-1095 (2003).

3. Xiang, Z., Pogozheva, I.D., Sorenson, N.B., et al. Peptide and small molecules rescue the functional activity and agonist potency of dysfunctional human melanocortin-4 receptor polymorphisms. Biochemistry 46(28), 8273-8287 (2007).

4. Martin, W.J., McGowan, E., Cashen, D.E., et al. Activation of melanocortin MC4 receptors increases erectile activity in rats ex copula. Eur. J. Pharmacol. 454(1), 71-79 (2002).

5. Cepoi, D., Phillips, T., Cismowski, M., et al. Assessment of a small molecule melanocortin-4 receptor-specific agonist on energy homeostasis. Brain Res. 1000(1-2), 64-71 (2004).