PF-00446687 

PF-00446687 is a potent, selective melanocortin-4 receptor (MC4R) agonist with EC50 of 12 ± 1 nM^[1]. Pf-446687 is brain penetrant^[2].

EC50: 12 ± 1 nM (MC4R)^[1]

PF-00446687 binds MC4 receptor with a K_i of 27±4 nM. PF-00446687 has a relatively weak activity at the MC1, MC3, and MC5 receptors with EC₅₀s of 1.02±0.30 μM, 1.16±0.35 μM, and 1.98±0.20 μM, respectively. The broad off-target profiles of PF-00446687 are assessed in the CEREP Bioprint wide ligand screening panel, with the most potent binding activities being at the σ receptor (K_i=330 nM), the sodium ion channel (K_i=690 nM), and the muscarinic M2 receptor (K_i=730 nM)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Pf-446687 is highly selective for MC4R and is both brain penetrant and stable in vivo. Peripheral administration of the brain penetrant MC3/4R receptor peptide agonist, Melanotan II (MTII), and the highly selective, small molecule MC4R agonist, Pf-446687, enhances partner preference formation in the prairie vole, but not in the non-monogamous meadow vole^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

470.59

Solid

C₂₈H₃₆F₂N₂O₂

862281-92-3

O=C([C@H]1[C@H](C2=C(C=C(F)C=C2)F)CN(C(C)(C)C)C1)N3C[C@H]([C@](O)(C4=CC=CC=C4)[C@@H](C)C3)C

Room temperature in continental US; may vary elsewhere.

• [1]. Lansdell MI, et al. Discovery of a selective small-molecule melanocortin-4 receptor agonist with efficacy in a pilot study of sexual dysfunction in humans. J Med Chem. 2010 Apr 22;53(8):3183-97.  [Content Brief]

  [2]. Modi ME, et al. Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole. Neuropsychopharmacology. 2015 Jul;40(8):1856-65.  [Content Brief]