cos-1

MCL0020 is a potent and selective melanocortin MC4 receptor antagonist (IC50 values are 11.63, 1115, and >10,000 nM at MC4, MC3, and MC1 receptors, respectively). It significantly reverses stress-induced anorexia without affecting food intake in free-feeding rats and exhibits anxiolytic-like activity in vivo.

β-Endorphin (1-27) is an endogenous peptide that binds to μ-, δ-, and κ-opioid receptors (Kis = 5.31, 6.17, and 39.82 nM, respectively, in COS-1 cells expressing rat receptors). It binds to rat and mouse brain membrane preparations (IC50s = 1.1 and 5.7 nM, respectively) and induces chemotaxis of human monocytes in vitro when used at a concentration of 1 nM. Intracerebroventricular administration of β-endorphin (1-27) increases the latency to tail withdrawal in response to thermal stimulation in mice with a median antinociceptive dose (AD50) of 1,500 pmol per animal. It inhibits antinociception induced by β-endorphin in mice in response to thermal stimuli when administered at a dose of 65 pmol per animal. In rats, β-endorphin (1-27) does not affect drug-associated place preference when administered at doses up to 20 μg, i.c.v., but inhibits β-endorphin-induced place preference when administered at a dose of 10 μg per animal.

TIP39, a neuropeptide and an agonist for the parathyroid hormone receptor type 2 (PTH2R), effectively increases cAMP levels in COS-7 cells featuring recombinant PTH2R from humans or rats (EC50s = 0.5 and 0.8 nM, respectively), as well as in F-11 cells that naturally express PTH2R (EC50 = 1.15 nM). Furthermore, TIP39 at 1 nM halts the cell cycle at the G0/G1 phase and reduces Sox9 expression, a crucial regulator of cartilage differentiation, in CFK2 rat chondrocytes. Additionally, administering 100 pmol/animal of TIP39 reduces the immobility period in the forced swim test in mice, indicating a potential antidepressant effect.