Ipamorelin vs Sermorelin vs TH9507: The Growth Hormone Secretagogue Family

Research-use-only context. This article summarizes published third-party scientific literature and laboratory practice. It is not medical advice, not a therapeutic or performance claim, and not a usage guide. US Prime Peptides products are supplied strictly for in vitro laboratory research and are not for human or veterinary use.

Ipamorelin, sermorelin and TH9507 are grouped under the label "growth hormone secretagogues," but the label hides a split: two of them are fragments or analogs of a native hypothalamic hormone, and one is a synthetic peptide that mimics a stomach hormone. This article compares the three by receptor class, sequence length, modification, development and approval history, and literature maturity, and explains why two of the three are also the names of approved or formerly approved drugs.

The short answer: one family name, two receptor branches

Sermorelin and TH9507 both act at the GHRH receptor, the class B G-protein-coupled receptor cloned from rat pituitary by Mayo in 1992. Sermorelin is the first 29 residues of human GHRH; TH9507 is the full 44-residue GHRH with a short fatty-acyl group on its N-terminus. Ipamorelin acts at a different receptor entirely, GHS-R1a, the class A G-protein-coupled receptor cloned by Howard and colleagues in 1996 that was later shown to be the ghrelin receptor. It is a five-residue synthetic peptide with no relationship to GHRH.

Two of the three have been approved drugs. TH9507 is approved by the FDA as Egrifta. Sermorelin was approved by the FDA as Geref and was discontinued in 2008. Ipamorelin has never been approved anywhere. A research vial of any of the three is not the drug product and is supplied only for in vitro work. Compound-level detail is in the articles on sermorelin, TH9507 and ipamorelin.

The GHRH-receptor branch: sermorelin and TH9507

Human GHRH is a 44-residue amidated peptide. A 1986 review in Clinics in Endocrinology and Metabolism by Grossman, Savage and Besser recounts that it was first extracted from two pancreatic tumors and that shorter C-terminally truncated forms retain activity. Sermorelin is GHRH(1-29)-NH₂, the shortest fragment with full activity at the receptor; a 1999 BioDrugs review by Prakash and Goa describes it in exactly those terms. Its average mass is about 3,358 Da, and its sequence contains an asparagine at position 8 that deamidates and a methionine at position 27 that oxidizes, both of which show up as adjacent impurity peaks on an HPLC trace.

The chemical weakness of the native sequence is its N-terminus. A 1991 Hormone and Metabolic Research paper by Su and colleagues measured a half-life of about 13 minutes for GRF(1-29)-NH₂ in porcine plasma and identified GRF(3-29) as the main product, formed by dipeptidyl peptidase IV cleaving after Ala2. TH9507 addresses this not by changing residues but by capping the N-terminal tyrosine with a trans-3-hexenoyl group. The 2007 Basic and Clinical Pharmacology and Toxicology paper by Ferdinandi and colleagues that reports the non-clinical pharmacology of TH9507 (TH9507's development code) states that this single modification made the peptide resistant to dipeptidyl peptidase IV and slowed its degradation in rat, dog and human plasma. TH9507 keeps all 44 residues, so its average mass is about 5,136 Da, and it retains the Asn8 and Met27 liabilities of the native sequence.

The ghrelin-receptor branch: ipamorelin

Ipamorelin is Aib-His-D-2-Nal-D-Phe-Lys-NH₂, average mass about 711.9 Da. It contains one non-proteinogenic residue (alpha-aminoisobutyric acid) and two D-amino acids, which is why it is resistant to ordinary proteases without any acyl or albumin tail. The 1998 European Journal of Endocrinology paper by Raun and colleagues that introduced it reports an EC₅₀ of 1.3 nM for growth hormone release from rat primary pituitary cells and describes the compound as having been selected from a series lacking the central Ala-Trp of GHRP-1. The same paper reports that in swine ipamorelin did not raise ACTH or cortisol at concentrations that released growth hormone, in contrast to GHRP-2 and GHRP-6, which is the basis for the word "selective" in its title.

Because GHS-R1a couples mainly through G_q and calcium, while the GHRH receptor couples through G_s and cyclic AMP, ipamorelin and the two GHRH-type peptides are not interchangeable in a receptor assay. They are different ligands for different receptors that happen to be expressed on the same somatotroph. Our CJC-1295 vs ipamorelin comparison covers the synergy literature behind pairing the two receptor classes.

Side-by-side comparison

The table shows that the three span a seven-fold range of mass, two receptor classes, and the full range of regulatory outcomes, from never submitted to currently approved. "Growth hormone secretagogue" is a functional label, not a chemical family.

Development and approval history

Sermorelin was developed in the 1980s as a diagnostic agent and later for pediatric use; the Prakash and Goa review summarizes that history and the human literature behind it. The FDA approval as Geref was withdrawn from the market in 2008 for commercial reasons rather than a safety finding, which is why sermorelin now exists in the US only as a research-grade material and as a compounded product in some settings. TH9507, developed by Theratechnologies as TH9507, was approved by the FDA in November 2010; the one-page 2011 Nature Reviews Drug Discovery note by Grunfeld, Dritselis and Kirkpatrick records the approval, and the 2012 Annals of Pharmacotherapy review by Spooner and Olin summarizes the clinical program. Ipamorelin was carried through early clinical work by Novo Nordisk and later by Helsinn, and neither program reached a marketing application.

The research-vial distinction matters most for TH9507. Egrifta is a specific approved formulation with its own specification; a lyophilized research vial labeled "TH9507" shares the sequence and the hexenoyl cap but is not that product, is not made under that specification, and carries only its own certificate of analysis. The article on FDA status of common research peptides tabulates this across the catalog.

What the literature covers for each

The three literatures differ in size and kind. For ipamorelin the published base is a 1998 rat-cell and swine characterization (Raun), a 1998 rat pharmacokinetic comparison with GHRP-2 and GHRP-6 (Johansen and colleagues, Xenobiotica), and later rodent work; human data are sparse. For sermorelin the base is decades of human endocrine-testing literature plus the receptor cloning and plasma-stability chemistry already cited. For TH9507 the base is the Ferdinandi non-clinical paper in rats, dogs and pigs, followed by a multi-trial human phase 3 program. The important asymmetry for a laboratory is that TH9507's human literature is tied to an approved drug product and says nothing about a research vial from another source, while ipamorelin's literature is almost entirely preclinical.

What the certificate must show for each

For a 5-residue peptide like ipamorelin, mass spectrometry gives a single clean species near 712 Da and HPLC usually shows one dominant peak; what mass spectrometry cannot confirm is the D-configuration at positions 3 and 4, since enantiomers have identical mass. For the two GHRH-type peptides the identity line typically shows multiply charged ions that deconvolute to the intact mass near 3,358 Da or 5,136 Da, and the chromatogram should be read for the deamidated (+1 Da) and oxidized (+16 Da) shoulders that Asn8 and Met27 produce. For TH9507 the certificate should also confirm that the hexenoyl cap is present, which shows up as a 96 Da difference from uncapped GHRH(1-44). US Prime Peptides posts lot-matched certificates for Ipamorelin 10 mg, Sermorelin 10 mg and TH9507 10 mg before purchase, each reporting identity, HPLC purity, net peptide content, endotoxin, sterility and heavy metals from an independent US laboratory.

Frequently Asked Questions

What is the difference between sermorelin and TH9507?

Sermorelin is the first 29 residues of human GHRH with a C-terminal amide and no other change. TH9507 is all 44 residues of GHRH with a trans-3-hexenoyl group on the N-terminal tyrosine, which makes it resistant to dipeptidyl peptidase IV. Both bind the GHRH receptor; they differ in length, mass (about 3,358 vs 5,136 Da) and approval status.

Does ipamorelin work on the same receptor as sermorelin?

No. Ipamorelin binds GHS-R1a, the ghrelin receptor, a class A GPCR that signals mainly through calcium. Sermorelin and TH9507 bind the GHRH receptor, a class B GPCR that signals through cyclic AMP. The receptors are on the same pituitary cell type but are unrelated proteins.

Is TH9507 an approved drug?

Yes. TH9507 is approved by the FDA as Egrifta (November 2010). A lyophilized research vial labeled TH9507 is not that product and is supplied only for in vitro laboratory use.

Was sermorelin ever approved by the FDA?

Yes. Sermorelin was approved by the FDA as Geref and was discontinued in 2008. A research vial of sermorelin is not Geref and is not an approved drug today.

Citations

1. Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol. 1992;6(10):1734-1744. PMID 1333056
2. Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974-977. PMID 8688086
3. Grossman A, Savage MO, Besser GM. Growth hormone releasing hormone. Clin Endocrinol Metab. 1986;15(3):607-627. PMID 2429796
4. Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs. 1999;12(2):139-157. PMID 18031173
5. Su CM, Jensen LR, Heimer EP, et al. In vitro stability of growth hormone releasing factor (GRF) analogs in porcine plasma. Horm Metab Res. 1991;23(1):15-21. PMID 1826667
6. Ferdinandi ES, Brazeau P, High K, et al. Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic Clin Pharmacol Toxicol. 2007;100(1):49-58. PMID 17214611
7. Grunfeld C, Dritselis A, Kirkpatrick P. TH9507. Nat Rev Drug Discov. 2011;10(2):95-96. PMID 21283099
8. Spooner LM, Olin JL. TH9507: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy. Ann Pharmacother. 2012;46(2):240-247. PMID 22298602
9. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561. PMID 9849822
10. Johansen PB, Hansen KT, Andersen JV, et al. Pharmacokinetic evaluation of ipamorelin and other peptidyl growth hormone secretagogues with emphasis on nasal absorption. Xenobiotica. 1998;28(11):1083-1092. PMID 9879640

This article is for laboratory research reference only. US Prime Peptides products are supplied strictly for in vitro research. Not for human consumption.

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