Pharmacological Characterization of Human Melanocortin-4 Receptor Polymorphisms and Targeted Functional Rescue by Ligands

摘要

Single nucleotide polymorphisms (SNPs) of the human melanocortin-4 receptor (MC4R) have been discovered in both obese and non-obese human patients [1,2]. Our research has focused upon the in vitro pharmacological characterization of over 60 hMC4R SNPs (Figure 1) to determine the potential molecular mechanism(s) that might associate a particular SNP with obesity [3,4,5]. These potential molecular mechanisms include; 1) not expressed at the cell surface, 2) changing endogenous ligand molecular recognition, and 3) changing endogenous ligand functional signaling (agonist and/or antagonist).