Growth Hormone Secretagogues Mapped: CJC-1295, Ipamorelin, Sermorelin and Relatives

All peptides in this group influence growth hormone release, yet they work through two completely different receptors: GHRH analogs bind the GHRH receptor on somatotrophs, while GHRPs bind the ghrelin receptor GHS-R1a. Once you sort the catalogue along that line — instead of by marketing label — the whole field becomes clear in a couple of minutes.

Two distinct families

Molecular weight alone reveals the split: the GHRH analogs fall between 3.3 and 5.1 kDa since they derive from a 44-residue hormone, whereas the GHRPs stay below 900 Da as short synthetic sequences containing unnatural residues — structurally unrelated to ghrelin, even though they act at its receptor.

How each family affects the axis

Activating the GHRH receptor influences how large the natural pulse is: it boosts somatotroph output but cannot overrule the somatostatin brake that decides when release happens. A GHRH analog thus operates inside the existing pulsatile pattern instead of replacing it.

Activating GHS-R1a works differently. The ghrelin receptor both triggers somatotroph release directly and dampens somatostatin tone, which is why GHRPs are said to influence how often pulses occur as well as how big they are. Because the mechanisms do not overlap, researchers study the two families in combination: going back to the classic secretagogue papers, a GHRH analog paired with a GHRP was reported to release more growth hormone than either on its own.

Selectivity sets the GHRPs apart

The four ghrelin receptor agonists in the catalogue all act on one receptor; what distinguishes them is their additional activity.

• Ipamorelin is the selective member. It is reported to release growth hormone while barely affecting cortisol and prolactin, which is why most combination study designs that need a clean readout include it.
• GHRP-2 is more potent at the receptor, but reportedly causes more collateral endocrine activity.
• GHRP-6 stands out for strong appetite-related signalling, in line with ghrelin’s orexigenic function — valuable if that is what you are studying, a confounder if it is not.
• Hexarelin is the most potent of the four and also binds CD36, giving it a body of cardiovascular research the others do not have. It is likewise the one most linked to receptor desensitisation after repeated exposure.

The selectivity trade-off is worked through in ipamorelin vs GHRP-2.

Half-life: the second dimension

How long receptors stay engaged differs by about three orders of magnitude across this range, and this is designed in, not accidental. Native GHRH disappears within minutes because dipeptidyl peptidase-4 cuts its N-terminus; sermorelin, as the unaltered fragment, shares that weakness. The four substitutions in the CJC-1295 backbone prevent the cut and stretch circulation time to hours. The DAC conjugate goes a step further, anchoring the peptide to serum albumin and turning a brief signal into one that lasts for days. Tesamorelin uses a third strategy, an N-terminal acyl group on the complete 44-residue sequence.

For research this means the molecules address different questions. A short-acting analog examines an acute, pulsatile response; a long-acting conjugate examines sustained receptor occupancy — a different physiological state, not just a handier version of the same one. The GHRPs, all small and quickly cleared, belong firmly to the acute end whichever one you pick.

The CJC-1295 naming confusion

This is the most stubborn source of confusion in the field, so it is worth being explicit. The name CJC-1295 first referred to a GHRH(1-29) analog carrying a drug affinity complex — a maleimidopropionyl linker that bonds covalently to albumin in the blood and greatly prolongs the half-life. In everyday research-supply language, however, "CJC-1295" on its own now normally denotes the tetra-substituted GHRH(1-29) analog without the linker, also known as Mod GRF (1-29).

These are two molecules with different pharmacokinetics: 3,367.93 Da without DAC and 3,647.28 Da with it — a 279 Da gap that a mass spectrum shows at a glance. The four substitutions both share, at positions 2, 8, 15 and 27, are there to withstand dipeptidyl peptidase cleavage and to limit chemical breakdown of the backbone. The head-to-head is in CJC-1295 vs CJC-1295 with DAC.

Very different regulatory positions

Legally, these peptides are far from equivalent — a surprise to anyone who assumes the category is uniform. Sermorelin was once an approved medicine and was later taken off the market for commercial, not safety, reasons. Tesamorelin is an approved prescription medicine for one specific indication and features in our catalogue solely as a prescription reference listing. Neither form of CJC-1295, nor ipamorelin, nor any of the GHRPs has ever been approved anywhere, and after FDA review of bulk substances several of them cannot be used in US pharmacy compounding. Across the entire family, research-grade material is supplied for laboratory use only.

Selecting reference standards

For questions about GHRH receptor pharmacology, the options are a native fragment (sermorelin, nearest to the endogenous hormone), a protease-resistant analog (CJC-1295 no DAC, longer-lasting without albumin binding) and a long-acting conjugate (CJC-1295 with DAC). For questions about ghrelin receptor pharmacology, the decision mainly concerns selectivity: ipamorelin is the clean probe, the others intentionally less selective tools.

Fixed-ratio blends are available for combination designs — CJC-1295 (no DAC) + ipamorelin is the pairing used most — and the usual trade-off applies: a blend locks the ratio, while separate vials let you vary one component. The family is catalogued at GHRPs and secretagogues.

A calculation reminder when comparing across families: 5 mg of ipamorelin corresponds to roughly 7.02 µmol, while 5 mg of tesamorelin corresponds to roughly 0.97 µmol — about seven times fewer moles for the same labelled mass. Always think in molar terms.