Table 3.

MC4R agonists studied in human clinical studies for various indications.

MC4R agonist, sponsor	Molecule type	Indication	Route of administration	Clinical efficacy	Dose administered	Side effects	Current status	Reference
Melanotan II, University of Arizona	7-amino acid cyclic peptide	Male erectile dysfunction	Subcutaneous	Human efficacy demonstrated	0.25 mg/kg, bolus	Increased cardiovascular (CV) activity, nausea, and vomiting	Development discontinued	[223]
Bremelanotide (PT141), Palatin Inc	7-amino acid cyclic peptide	Male erectile dysfunction (MED) and pre-menopausal hypoactivity sexual desire disorder (HSDD)	Subcutaneous	Efficacious in both indications	HSDD: 175 mg, bolus	MED: Increased CV activity, nausea, and vomiting HSAD: Therapeutic index established against cardiovascular side effects	Marketed for HSDD (trade name Vyleesi)	[224,231]
PF-00446687, Pfizer Inc	Small molecule	MED and post-menopausal HSDD	Oral	Efficacious in both indications	MED: 200 mg HSDD: 200 mg	Not disclosed	Unknown	[225]
MK-0493, Merck	Small molecule	Obesity	Oral	No efficacy observed	200–1000 mg	None; well tolerated	Development discontinued	[226]
LY2112688, Eli Lilly	8-amino acid cyclic peptide	Obesity	Subcutaneous infusion	No efficacy observed	0.5, 0.15, 0.45, and 1 mg infused over 24 h 0.15, 0.45, 1, and 2 mg/day for 7 days	Increased CV and erectile activity	Development discontinued	[227]
MC4-NN-0453, Novo Nordisk	12 amino acid peptide with a modified lipid chain	Obesity	Subcutaneous	Lack of weight loss	Single dose study: 0.3–15 mg/kg Multi-dose study: 0.75–30 mg/kg	Skin tanning and sexual arousal disturbances	Development discontinued	[228]
AZD2820a, AstraZeneca	Undisclosed	Obesity	Subcutaneous	Undisclosed	Undisclosed	Serious adverse events related to allergic reactions	Development discontinued	[232]
Setmelanotide, Rhythm Pharmaceuticals	8-amino acid cyclic peptide	Genetic obesity	Subcutaneous	Efficacy established in completed phase II and phase III studies	1–3 mg bolus per day	No increase in CV activity. Selected common side effects can include hyperpigmentation, nausea/vomiting, penile erection, and injection site reactions	Currently under evaluation for treating obesity-associated MC4R pathway deficiencies	[5,229,230,233,234]

^aPartial agonist in MC4R.