Sermorelin
[CAS# 86168-78-7]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Other protected amino acids
• Name: Sermorelin
• Synonyms: 3S)-4-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-4-oxobutanoic acid
• Molecular Formula: C₁₄₉H₂₄₆N₄₄O₄₂S
• Molecular Weight: 3357.88
• Protein Sequence: YADAIFTNSYRKVLGQLSARKLLQDIMSR
• CAS Registry Number: 86168-78-7
• SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC3=CC=C(C=C3)O)N

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Index of refraction: 1.65 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovery and Applications

Sermorelin is a synthetic peptide analogue of growth hormone-releasing hormone (GHRH), consisting of the first 29 amino acids of the endogenous human GHRH_1–44. This portion of the full hormone retains full biological activity and was identified as the shortest functional fragment capable of stimulating the release of growth hormone (GH) from the anterior pituitary gland. The development of sermorelin originated from efforts in the late 1970s and early 1980s to better understand the regulatory mechanisms of GH secretion and to explore potential therapeutic applications for disorders of growth deficiency.

The original discovery of GHRH in human hypothalamic tissue led to the subsequent synthesis of active fragments. Among these, sermorelin was shown to mimic the natural physiological effects of GHRH by binding to the GHRH receptor in the pituitary. Upon binding, it triggers the cAMP second messenger pathway, promoting synthesis and pulsatile release of GH. This made sermorelin a useful tool for diagnostic testing of pituitary function and as a potential therapy for conditions characterized by GH deficiency.

Sermorelin was first approved by the U.S. Food and Drug Administration (FDA) for use in pediatric patients with idiopathic growth hormone deficiency. In clinical practice, it was used to assess the ability of the pituitary gland to produce GH, helping to differentiate between hypothalamic and pituitary causes of growth disorders. Compared to direct administration of recombinant GH, sermorelin stimulates the physiological GH axis, thereby maintaining feedback regulation by somatostatin and reducing the risk of supraphysiological hormone levels.

Over time, sermorelin gained interest for potential use beyond pediatric endocrinology, including in adult GH deficiency, age-related hormonal decline, and in attempts to enhance physical performance or body composition. However, such applications were not approved by regulatory authorities, and available evidence was often insufficient to establish consistent clinical benefits in these contexts.

Pharmacokinetically, sermorelin has a short plasma half-life, typically under 20 minutes following intravenous administration. It is rapidly metabolized by plasma proteases and cleared predominantly through renal filtration. Because of this, its clinical application often required frequent or continuous infusion to maintain desired GH release profiles. The synthetic peptide is usually administered subcutaneously.

Although sermorelin was once commercially available for therapeutic use, it was eventually discontinued in the U.S. market, not due to safety concerns but rather due to business and market factors. Its use persists in research settings and compounding pharmacies, particularly in regions where off-label prescribing is permitted. Its function continues to be of interest in studies related to endocrinology and aging, especially where stimulation of endogenous GH secretion is preferable to exogenous GH replacement.

Chemically, sermorelin has the molecular formula C₁₄₉H₂₄₆N₄₄O₄₂ and a molecular weight of approximately 3357.9 g/mol. The amino acid sequence of sermorelin is: H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH₂. As a peptide drug, it must be handled carefully to preserve stability, typically requiring storage at or below -20 °C and reconstitution with sterile aqueous solutions prior to use.

Sermorelin has played a notable role in advancing the understanding of hypothalamic-pituitary signaling and has contributed to clinical methodologies for diagnosing and managing growth hormone deficiencies. While its availability in mainstream medicine has diminished, it remains relevant in specialized medical and research settings, where it continues to serve as a model compound for evaluating the therapeutic modulation of GH secretion.

References

1984. Super-active analogs of growth hormone-releasing factor (1-29)-amide. Biochemical and Biophysical Research Communications, 119(1).
DOI: 10.1016/0006-291x(84)91647-4

2018. Inhibition of experimental small‐cell and non‐small‐cell lung cancers by novel antagonists of growth hormone‐releasing hormone. International Journal of Cancer, 142(11).
DOI: 10.1002/ijc.31308

2021. Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug Testing and Analysis, 13(11).
DOI: 10.1002/dta.3183