While a huge amount of specific synthetic or peptidic ligands, including setmelanotide [53,54,55,56], bivalent ligands [57,58,59,60], and many others [61,62,63], have been designed, there is a tremendous medical as well as socioeconomic interest in the development of functionally optimized (tailor-made for specific signaling pathways) MC4R ligands reasoned by an increasing prevalence of human obesity worldwide [64]. This evidence concerns the gene MC4R and obesity disorder.