Pharmacology
Setmelanotide binds to and activates MC4 receptors in the paraventricular nucleus (PVN) of the hypothalamus and in the lateral hypothalamic area (LHA), areas involved in the regulation of appetite, and this action is thought to underlie its appetite suppressant effects. In addition to reducing appetite, setmelanotide increases resting energy expenditure in both obese animals and humans. Importantly, unlike certain other MC4 receptor agonists, such as LY-2112688, setmelanotide has not been found to produce increases in heart rate or blood pressure.Setmelanotide has been reported to possess the following activity profile (cAMP, EC50): MC4 (0.27 nM) > MC3 (5.3 nM) ≈ MC1 (5.8 nM) > MC5 (1600 nM) ≟ MC2 (>1000 nM). (19.6-fold selectivity for MC4 over MC3, the second target of highest activity.) History
Setmelanotide was invented at Ipsen by Jesse Z. Dong. It was initially known as BIM-22493 and then as RM-493 and IRC-022493. It was evaluated in two one-year clinical studies. The first study enrolled 10 participants with obesity and confirmed or suspected POMC or PCSK1 deficiency while the second study enrolled 11 participants with obesity and confirmed or suspected LEPR deficiency; all participants were six years or older. Most participants had lost more than 10% of their initial body weight after a year of treatment. Some participants also reported feeling less hungry.The U.S. Food and Drug Administration (FDA) granted the application for setmelanotide orphan disease designation, breakthrough therapy designation, and priority review.
The same study also found that both dermal exposure to EDTA in most cosmetic formulations and inhalation exposure to EDTA in aerosolised cosmetic formulations would produce exposure levels below those seen to be toxic in oral dosing studies. Synthesis
The compound was first described in 1935 by Ferdinand Münz, who prepared the compound from ethylenediamine and chloroacetic acid. Today, EDTA is mainly synthesised from ethylenediamine (1,2-diaminoethane), formaldehyde, and sodium cyanide. This route yields the tetrasodium EDTA, which is converted in a subsequent step into the acid forms:

H2NCH2CH2NH2  +  4 CH2O  +  4 NaCN  +  4 H2O   →  (NaO2CCH2)2NCH2CH2N(CH2CO2Na)2  +  4 NH3(NaO2CCH2)2NCH2CH2N(CH2CO2Na)2  +  4 HCl  →  (HO2CCH2)2NCH2CH2N(CH2CO2H)2  +  4 NaClThis process is used to produce about 80,000 tonnes of EDTA each year. Impurities cogenerated by this route include glycine and nitrilotriacetic acid; they arise from reactions of the ammonia coproduct. Nomenclature
To describe EDTA and its various protonated forms, chemists distinguish between EDTA4−, the conjugate base that is the ligand, and H4EDTA, the precursor to that ligand. At very low pH (very acidic conditions) the fully protonated H6EDTA2+ form predominates, whereas at very high pH or very basic condition, the fully deprotonated EDTA4− form is prevalent. In this article, the term EDTA is used to mean H4−xEDTAx−, whereas in its complexes EDTA4− stands for the tetraanion ligand. Coordination chemistry principles
In coordination chemistry, EDTA4− is a member of the aminopolycarboxylic acid family of ligands.