receptor is exposed to extracellular concentrations (~1.2 mM in the extracellular space of the central nervous system) but might not be bound intracellularly ( concentration: 100 nm), thus suggesting a potential regulatory role for in α-MSH–binding dynamics. Signaling along the phospholipase C pathway can significantly raise the intracellular concentration, and this may constitute positive feedback from signaling of MC4 receptor or other receptors that result in flux. This discovery highlights the plasticity and multipronged regulation and control of this receptor and will aid in next-generation structure-based drug design of therapeutics for MC4R-related obesity. Ligands Agonists Non-selective α-MSH β-MSH γ-MSH ACTH Afamelanotide Bremelanotide Melanotan II Modimelanotide Setmelanotide was approved by FDA as first-ever therapy for chronic weight management (IMCIVREE).The setmelanotide was advanced first-in-class, precision medicine that is designed to directly address the underlying cause of obesities driven by genetic deficits in the melanocortin-4 (MC4) receptor pathway. Selective AZD2820 LY-2112688 MK-0493 PF-00446687 PG-931 PL-6983 Ro 27-3225 – also some activity at MC1 THIQ Antagonists Non-selective Agouti-related peptide Agouti signalling peptide SHU-8914 SHU-9005 SHU-9119 Selective HS-014 HS-024 JKC-363 MCL-0020 MCL-0042 – also a serotonin reuptake inhibitor MCL-0129 ML-00253764 MPB-10 Unknown Semax See also Melanocortin receptor References Further reading External links G protein-coupled receptors Human proteins