. Author manuscript; available in PMC: 2017 Nov 9.

Published in final edited form as: J Med Chem. 2016 Mar 29;59(7):3112–3128. doi: 10.1021/acs.jmedchem.5b01894

Table 3. Summary of functional experiments for based compounds evaluated at the mouse melanocortin receptors.

	mMC1R		mMC3R		mMC4R		mMC5R
Compound	Agonist (EC₅₀)		Agonist (EC₅₀)	Antagonist (pA₂)	Agonist (EC₅₀)	Antagonist (pA₂)	Agonist (EC₅₀)
	Mean±SEM	Fold	Mean±SEM	Mean±SEM	Mean±SEM	Mean±SEM	Mean±SEM
9	98.4±32.2^*	1	45% at 100 μM	6.04±0.09	40% at 100 μM	8.09±0.04	75% at 100 μM
10	112±19	0.9	40% at 100 μM^*	6.14±0.06	20% at 100 μM^*	8.39±0.08	PA, 70% at 100 μM
11	139±17^*	0.7	PA, 50% at 100 μM^*	6.07±0.18	40% at 100 μM^*	7.97±0.29	PA, 65% at 100 μM^*
12	563±142^*	0.2	80% at 100 μM^*	6.08±0.11	85% at 100 μM^*	7.68±0.37	786±185^*

AlphaScreen® assays were performed to determine relative potency of compounds to induce cAMP signaling. The reported errors are the standard error of the mean (SEM) of at least three independent experiments. Antagonist activity was evaluated at only the mMC3R and mMC4R with all compounds based on the His-DNal(2′)-Arg-Trp pharmacophore. The pA₂ values were calculated by a Schild analysis in which NDP-MSH was in a standard dose response (10^-12 to 10^-6) and three doses of antagonist were used to shift the agonist dose response. PA indicates partial agonist activity was observed. Percentage (%) indicate the amount of activity relative to maximal NDP-MSH response was observed at 100 μM.

denotes six or more independent experiments. A bar graph representation of the partial functional responses and the associated error can be seen in the supplemental information.