PF-00446687 is a drug developed by Pfizer for the treatment of erectile dysfunction, which is a non-peptide agonist selective for the melanocortin receptor subtype MC4. It was found to be active in preliminary human trials, with the 200mg dose being of similar effectiveness to 100mg sildenafil, though lower doses were ineffective. While it is unclear whether PF-00446687 itself will be potent and effective enough to be developed for medical use, it has demonstrated that selectively targeting the MC4 subtype can produce similar aphrodisiac effects to older non-selective peptide-based melanocortin receptor agonists like melanotan II and bremelanotide, without the side effects caused by action at the other melanocortin receptor subtypes.
^Calabrese et al. (3,5-DIMETHYLPIPERIDIN-1-YL)(4-PHENYLPYRROLIDIN-3-YL)METHANONE DERIVATIVES AS MCR4 AGONISTS. US Patent 7649002, Jan 19th 2010.
^Lansdell MI, Hepworth D, Calabrese A, Brown AD, Blagg J, Burring DJ, Wilson P, Fradet D, Brown TB, Quinton F, Mistry N, Tang K, Mount N, Stacey P, Edmunds N, Adams C, Gaboardi S, Neal-Morgan S, Wayman C, Cole S, Phipps J, Lewis M, Verrier H, Gillon V, Feeder N, Heatherington A, Sultana S, Haughie S, Martin SW, Sudworth M, Tweedy S. Discovery of a selective small-molecule melanocortin-4 receptor agonist with efficacy in a pilot study of sexual dysfunction in humans. Journal of Medicinal Chemistry. 2010 Apr 22;53(8):3183-97. PMID 20329799