Ipamorelin

A pentapeptide built on non-standard residues: aminoisobutyric acid at position 1, then D-2-naphthylalanine and D-phenylalanine, with an amidated C-terminus. Drawn in the PepXtide structural library, where its computed mass matches the published molecular weight.

Despite sitting in the same catalogue category as the releasing-factor analogues, this compound is not related to them. It is not a fragment of growth hormone releasing hormone and shares no sequence homology with it. It was developed at Novo Nordisk and first described in 1998 as the first selective growth hormone secretagogue, identified from a series of compounds derived from the growth-hormone-releasing-peptide chemotype and lacking the central alanine-tryptophan dipeptide of GHRP-1.

Four of its five positions are unusual. Position one is alpha-aminoisobutyric acid, a non-proteinogenic residue whose two methyl groups on the alpha carbon severely restrict backbone rotation. Position three is D-2-naphthylalanine and position four is D-phenylalanine, both of the D configuration, and the C-terminus is an amide rather than a free acid. Only the histidine at position two and the lysine at position five are ordinary L-amino acids. D-residues are not substrates for the peptidases that recognise L-configured backbones, which is the general reason this architecture is used, though the primary literature does not name a specific protease that each substitution was chosen to resist.

The molecular target is the growth hormone secretagogue receptor type 1a, also called the ghrelin receptor, a 366-residue class A G-protein-coupled receptor of the rhodopsin family that signals through phospholipase C to inositol phosphates and calcium mobilisation. This is a different receptor and a different signalling route from the class B, cyclic-AMP-coupled GHRH receptor used by sermorelin, tesamorelin and the CJC-1295 analogues, which is the substantive distinction within this category.

Reported in-vitro values give a binding affinity of about 63 nM at the receptor expressed in COS-7 cells, and a half-maximal effective concentration of roughly 1.3 nM in the primary rat pituitary cell assay historically used to rank secretagogues, against about 2.2 nM for GHRP-6 in the same system. The word selective in the original title refers to the receptor and hormone-axis selectivity reported in that characterisation relative to earlier compounds of the class.

Supplier technical data report solubility of about 20 mg/mL in dimethylformamide and dimethyl sulfoxide, about 30 mg/mL in ethanol and about 10 mg/mL in phosphate-buffered saline at pH 7.2, with storage at -20C. Published plasma-stability half-life figures for this compound specifically were not located in the primary literature.