Sermorelin

Overview

Sermorelin is GHRH(1-29) amide — the first twenty-nine residues of growth hormone-releasing hormone, with an amidated C-terminus and no other modification. It is the unembellished form of the molecule that the rest of this library’s GHRH compounds are built from.

It is not part of our catalogue. It is documented because without it the others do not make sense: Mod GRF 1-29, CJC-1295 with DAC and Tesamorelin are all answers to problems that sermorelin has.

Chemical identity

• Also known as: GHRH(1-29) amide, GRF(1-29), Geref
• CAS number: 86168-78-7
• Molecular formula: C₁₄₉H₂₄₆N₄₄O₄₂S
• Molecular weight: 3357.9 g/mol
• Classification: GHRH analogue, GHRH receptor agonist
• Length: 29 residues, C-terminally amidated

At 3,358 g/mol it is well past the size where a structure diagram remains readable. The single sulfur is one methionine — the residue that Mod GRF 1-29 substitutes out.

Why twenty-nine

Native GHRH is 44 residues. Structure–activity work established that biological activity resides almost entirely in the N-terminal portion, and that the first 29 residues are sufficient for full receptor activation. Residues 30 to 44 contribute little that can be measured at the receptor.

Sermorelin is that finding made concrete: the shortest fragment retaining full activity, with a C-terminal amide replacing the free acid that truncation would otherwise leave. The amidation is a minimal courtesy rather than a redesign — it removes a charge the natural sequence does not have at that position.

Everything else about the molecule is native GHRH.

The family tree

Laid out in order, the GHRH compounds in this library form a clear progression of escalating engineering, and sermorelin sits at its root:

• Sermorelin — GHRH(1-29) amide. No protective modifications. Half-life on the order of minutes.
• Mod GRF 1-29 — sermorelin plus four substitutions: D-alanine at 2 to block DPP-4, glutamine at 8 against deamidation, alanine at 15 for potency, leucine at 27 against oxidation. Half-life roughly thirty minutes.
• CJC-1295 with DAC — Mod GRF plus a lysine at 30 carrying a maleimide that binds albumin covalently. Half-life six to eight days.
• Tesamorelin — the alternative route entirely: the full 44-residue sequence with an N-terminal cap rather than a truncated and rebuilt fragment.

Read in sequence, each compound is the previous one with a specific liability addressed. Sermorelin’s liability is that it does not last, and the entire family downstream of it exists to fix that.

Short duration as a property, not only a defect

Sermorelin is cleared within minutes, cut by DPP-4 at the same position as native GHRH. Every modification in the compounds above exists to prevent that.

But brevity is not purely a disadvantage, and this is worth stating because the compounds that fixed it are usually presented as straightforward improvements.

Growth hormone is secreted in discrete bursts with near-undetectable troughs between them, and that pattern is physiologically meaningful — receptor responsiveness and downstream signalling respond differently to pulses than to sustained elevation. A compound cleared in minutes produces something close to a natural pulse. A compound with a week-long half-life does not; it produces continuous stimulation with pulses superimposed.

So for a study whose subject is physiological pulse patterning, the unmodified fragment is arguably the more faithful tool, and the engineered versions trade fidelity for convenience. Which matters depends entirely on the question.

Regulatory status

Sermorelin was an approved prescription medicine, marketed as Geref for growth hormone deficiency in children, and also used as a diagnostic agent for pituitary function.

It was subsequently withdrawn from the market. The withdrawal was a commercial decision rather than a safety action — recombinant growth hormone had become the standard treatment, and a product stimulating endogenous release occupied a shrinking niche.

That distinction matters when reading about the compound. A withdrawn medicine and a medicine withdrawn for safety reasons are very different things, and secondary sources are not always careful about which one this was.

Handling and storage

• Methionine oxidation is the principal chemical vulnerability — the one that Mod GRF 1-29’s leucine substitution was designed to remove. This molecule still has it.
• Asparagine deamidation is the second, also addressed downstream by the glutamine substitution. Sermorelin is measurably less stable in storage than its engineered descendants, which is a direct consequence of being unmodified.
• Lyophilised storage: sealed, refrigerated, protected from light; freeze for long-term storage.
• Reconstitution: add diluent slowly down the vial wall, allow to dissolve undisturbed, do not shake.

Purity and analytical verification

Twenty-nine coupling steps generate a substantial population of deletion sequences, so HPLC purity is doing real work here.

What sermorelin does not have is the verification problem that afflicts its descendants. Mod GRF 1-29’s D-alanine at position 2 is invisible to mass spectrometry, because an enantiomer has an identical mass — so a certificate cannot confirm the modification that matters most. Sermorelin has no D-amino acids, no unnatural residues and no conjugation. It is a native sequence, and mass plus purity genuinely characterise it.

There is a certain irony in that: the unmodified parent is easier to verify than the engineered compounds that improved on it, precisely because it has nothing engineered to get wrong.

References

• Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs, 1999. PMID 18031173
• Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clinical Interventions in Aging, 2006. PMID 18046908

Summary

Sermorelin is GHRH(1-29) amide, CAS 86168-78-7, molecular formula C₁₄₉H₂₄₆N₄₄O₄₂S, molecular weight 3,357.9 g/mol — the shortest fragment of growth hormone-releasing hormone retaining full receptor activity, with no protective modifications. It is the parent of the entire GHRH family documented here: Mod GRF 1-29 adds four substitutions to it, CJC-1295 with DAC adds albumin conjugation on top of those, and Tesamorelin solves the same problem from the opposite direction. Cleared within minutes, it produces the most physiologically faithful growth hormone pulse of the group, which makes its principal weakness a genuine advantage for some study designs. It was an approved medicine, withdrawn commercially rather than for safety. We do not stock it.

This page is provided for research reference. Compounds described in this library are for laboratory research use only, are not drugs, foods or cosmetics, and may not be used for any purpose other than in vitro or non-human laboratory research.