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Ipamorelins selectivity for GH release over cortisol, ACTH, and prolactin co-stimulation is conferred primarily by its Aib (-aminoisobutyric acid) substitution a non-natural alpha-methyl amino acid that constrains the peptide backbone conformation in a manner that optimises GHS-R1a engagement at somatotrophs while reducing interactions with GHS-R1a expressing hypothalamic CRH neurons responsible for ACTH/cortisol co-stimulation

Ipamorelin, a new growth-hormone-releasing peptide, selectively stimulates GH release in healthy men. Journal of Clinical Endocrinology & Metabolism, 86(8), 38773883

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