Classification
- Ipamorelin
- GHRP — growth hormone releasing peptide
- Sermorelin
- GHRH analog
Compound comparison
Ipamorelin vs Sermorelin
Two receptors, two scales. Ipamorelin is a five-residue GHSR-1a agonist signalling through calcium; sermorelin is the unmodified 29-residue GHRH(1-29) fragment acting at GHRH-R through cAMP-PKA and cleared within ten to twenty minutes. Sermorelin was approved as Geref and withdrawn; ipamorelin stopped at phase 2. Cortisol-sensitive designs favour ipamorelin’s selectivity; GHRH-arm designs use sermorelin.
Quick Answer
Five residues against twenty-nine, and two different receptors. Ipamorelin is a 711.9 Da pentapeptide (CAS 170851-70-4) that agonises GHSR-1a, the ghrelin receptor, through calcium mobilisation. Sermorelin is the native GHRH(1-29) fragment at 3,357.9 Da (CAS 86168-78-7), acting at GHRH-R through cAMP-PKA. They converge on the same somatotroph by separate routes, which is why combination designs outnumber head-to-head ones. No trial has compared them directly.
Ipamorelin
Sermorelin
Compound Reference Pages
Ipamorelin vs Sermorelin: At a Glance
Receptor target
- Ipamorelin
- GHSR-1a (ghrelin receptor)
- Sermorelin
- GHRH-R (growth hormone-releasing hormone receptor)
Amino acid count
- Ipamorelin
- 5 (pentapeptide)
- Sermorelin
- 29
Sequence / structure
- Ipamorelin
- Aib-His-D-2-Nal-D-Phe-Lys-NH2
- Sermorelin
- GRF(1-29)-NH2, the native GHRH N-terminal fragment
CAS number
- Ipamorelin
- 170851-70-4
- Sermorelin
- 86168-78-7
Molecular formula
- Ipamorelin
- C38H49N9O5
- Sermorelin
- C149H246N44O42S
Molecular weight
- Ipamorelin
- 711.9 Da (PubChem CID 9831659)
- Sermorelin
- 3,357.9 Da (PubChem CID 16132413)
Signalling cascade
- Ipamorelin
- Gq/phospholipase C, calcium-mediated
- Sermorelin
- Gs/adenylate cyclase, cAMP-PKA
Cortisol and prolactin release
- Ipamorelin
- Minimal in the preclinical models where it was characterised, unlike GHRP-2 and GHRP-6
- Sermorelin
- Not a reported feature of GHRH-R agonism
Non-natural residues
- Ipamorelin
- Yes — Aib, D-2-Nal and D-Phe confer protease resistance
- Sermorelin
- No — unmodified native GHRH fragment
Reported plasma half-life
- Ipamorelin
- Not established in peer-reviewed human pharmacokinetic literature
- Sermorelin
- Short, on the order of 10 to 20 minutes in Geref-era pharmacokinetic reports
Highest published human trial stage
- Ipamorelin
- Phase 2; development discontinued, no approval
- Sermorelin
- Approved and marketed as Geref, since withdrawn from market
Age of the main literature
- Ipamorelin
- Late 1990s onward, predominantly preclinical
- Sermorelin
- Predominantly pre-2000, from the Geref development era
Commonly combined with
- Ipamorelin
- CJC-1295 No DAC (GHRH arm)
- Sermorelin
- Ghrelin-receptor agonists (GHSR arm)
Purity (Peptide.Express)
- Ipamorelin
- ≥99% by reverse-phase HPLC, batch CoA
- Sermorelin
- ≥99% by reverse-phase HPLC, batch CoA
Ipamorelin compared with Sermorelin across mechanism, structure and research attributes. Research reference only.
How Ipamorelin and Sermorelin Differ in Research
The most common mistake in comparing these two is treating them as alternatives. They act on different receptors on the same cell, and the physiological response to activating both simultaneously exceeds what either produces alone. In practice that means most research designs featuring one of them feature something from the other class as well.
Ipamorelin is the more chemically unusual of the two. At 711.9 Da it is tiny for a receptor-active peptide, and three of its five residues are non-natural: alpha-aminoisobutyric acid, D-2-naphthylalanine and D-phenylalanine. Those substitutions do two jobs — they resist proteolytic degradation, and they confer the receptor selectivity that separates ipamorelin from earlier GHRPs. GHRP-2 and GHRP-6 stimulate cortisol and prolactin alongside growth hormone; ipamorelin largely does not, which makes it a cleaner tool when cortisol is a confounder in the experimental design.
Sermorelin is the more conventional molecule: the N-terminal 29 residues of endogenous GHRH, unmodified, at 3,357.9 Da. The C-terminal 15 residues of the full 44-amino-acid hormone turn out to be unnecessary for receptor binding, which is why the truncated fragment retains activity. Being unmodified is also its limitation — with no N-terminal protection it is cleared quickly, on the order of ten to twenty minutes in Geref-era pharmacokinetic reports, against stabilised analogs like tesamorelin that carry modifications specifically to slow that degradation.
The evidence bases are asymmetric in an awkward way, and the asymmetry does not run cleanly in either direction. Sermorelin has a real approval history — it was marketed as Geref and has since been withdrawn, generally described as a commercial rather than a safety decision — but most of its literature predates 2000 and reflects assay methods and trial conventions of that era.
Ipamorelin has cleaner selectivity data and more modern receptor pharmacology, but a narrower body of work, a discontinued phase 2 programme and no approval anywhere. Neither has published human pharmacokinetics of the quality you would want before quoting a number, and no trial has compared the two against each other at any point.
Ipamorelin vs Sermorelin: Frequently Asked Questions
What is the difference between ipamorelin and sermorelin?
The receptor. Ipamorelin is a 5-amino-acid pentapeptide agonising GHSR-1a, the ghrelin receptor, through a calcium-mediated pathway. Sermorelin is a 29-amino-acid GHRH(1-29) analog acting at the GHRH receptor through the cAMP-PKA cascade. Both increase GH secretion; they arrive by different routes.
Is ipamorelin a GHRH analog?
No. Ipamorelin is a GHRP — a growth hormone releasing peptide that mimics ghrelin. Sermorelin, CJC-1295 and tesamorelin are the GHRH analogs.
Why is ipamorelin described as selective?
Because unlike earlier GHRPs such as GHRP-2 and GHRP-6, it produces minimal cortisol and prolactin release at research concentrations. That selectivity comes from the non-natural residues in its sequence, and it matters in any design where cortisol would confound the readout. It is concentration-dependent rather than absolute.
Can ipamorelin and sermorelin be studied together?
They can, and the rationale is the same as for the more common CJC-1295 plus ipamorelin pairing — two convergent pathways onto the same somatotroph. In practice CJC-1295 (No DAC) is used more often than sermorelin for the GHRH arm because of its improved stability.
Which has the longer half-life?
Only one side has a usable published figure, so the honest answer is that this cannot be settled. Sermorelin is an unmodified native GHRH fragment cleared on the order of ten to twenty minutes in Geref-era reports. Ipamorelin's human plasma half-life is not established in peer-reviewed pharmacokinetic literature, and its non-natural residues predict proteolytic resistance without measuring it.
Which has more published research behind it?
Neither convincingly. Sermorelin has the larger clinical footprint because it was an approved product, but most of that work predates 2000. Ipamorelin has more modern receptor pharmacology and a discontinued phase 2 programme. Both are thin by the standards of a compound with a current approval, and no head-to-head study exists.
Is sermorelin the same as Geref?
Geref was the brand name under which sermorelin held FDA approval. That approval has since been withdrawn from market, generally described as a commercial rather than a safety decision. Research-market sermorelin is not the approved pharmaceutical product.
What is the difference between sermorelin and tesamorelin?
Length and stability. Sermorelin is the unmodified 29-residue GHRH fragment at 3,357.9 Da. Tesamorelin is the full 44-residue GHRH sequence at 5,136 Da with a trans-3-hexenoyl group at the N-terminus that slows metabolic degradation. Tesamorelin holds a current FDA approval as Egrifta; sermorelin's approval as Geref has been withdrawn.
Are Ipamorelin and Sermorelin verified to the same grade?
Yes. Both are verified at ≥99% purity by reverse-phase HPLC with LC-MS/MS identity confirmation, and ship with a batch-specific Certificate of Analysis. For in-vitro laboratory research use only.
References
- Raun K, et al. "Ipamorelin, the First Selective Growth Hormone Secretagogue." European Journal of Endocrinology, 1998. Read the Raun ipamorelin selectivity study on PubMed
- Smith RG, et al. "Modulation of Pulsatile GH Release Through a Novel Receptor in Hypothalamus and Pituitary Gland." Recent Progress in Hormone Research, 1996. Read the GH secretagogue receptor and phospholipase C signaling review on PubMed
- Bowers CY, Momany FA, Reynolds GA, Hong A. "On the In Vitro and In Vivo Activity of a New Synthetic Hexapeptide That Acts on the Pituitary to Specifically Release Growth Hormone." Endocrinology, 1984. Read the founding Bowers GHRP hexapeptide study on PubMed
- Mayo KE. "Molecular Cloning and Expression of a Pituitary-Specific Receptor for Growth Hormone-Releasing Hormone." Molecular Endocrinology, 1992. Read the GHRH receptor cloning and cAMP-signaling study on PubMed
- Wehrenberg WB, Ling N. "In Vivo Biological Potency of Rat and Human Growth Hormone-Releasing Factor and Fragments of Human Growth Hormone-Releasing Factor." Biochemical and Biophysical Research Communications, 1983. Read the GRF fragment structure-activity study on PubMed
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