Tesamorelin is a synthetic analog of human growth hormone-releasing hormone (GHRH): the complete 44-residue GHRH sequence with a trans-3-hexenoyl group attached to the N-terminal tyrosine. That small acyl cap makes the peptide resistant to the plasma enzyme that normally inactivates GHRH within minutes, while it still binds and activates the GHRH receptor. Tesamorelin is approved by the FDA as Egrifta for one indication in adults with HIV, and it is also supplied as a research reagent.
This profile covers its sequence and identity data, the chemistry of the hexenoyl modification, how it compares with other GHRH analogs, the receptor it acts on, the models it was studied in, and its regulatory history.
Where tesamorelin comes from
GHRH was first isolated in 1982 from human pancreatic tumors that had caused acromegaly. Guillemin's group reported the 44-residue sequence, ending in a C-terminal leucine amide, and showed that the synthetic peptide had full activity in vitro and in vivo. UniProt entry P01286 places that 44-residue peptide within a 108-residue precursor, flanked by a signal peptide and two propeptides.
The native hormone has one serious weakness as a reagent. In 1986 Frohman and colleagues showed that plasma removes the first two residues, Tyr-Ala, converting GRH(1-44)-NH2 to GRH(3-44)-NH2, a fragment with less than a thousandth of the original activity. After intravenous delivery to volunteers, the intact peptide had a half-life of 6.8 minutes. The enzyme responsible, a dipeptidyl aminopeptidase, is now called DPP-4.
Tesamorelin, originally coded TH9507, was developed by Theratechnologies in Montreal to close that gap with the smallest possible change. Ferdinandi and colleagues described it in 2007 as hGRF(1-44)NH2 "minimally modified" by adding a trans-3-hexenoyl moiety to Tyr1.
Identity
| Property | Tesamorelin |
|---|---|
| Class | GHRH analog (GHRH receptor agonist) |
| Sequence | (trans-3-hexenoyl)-YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL-NH2 |
| Length | 44 residues plus the N-terminal acyl group, C-terminal amide |
| N-terminal modification | trans-3-hexenoyl, an (E)-hex-3-enoyl group: a six-carbon acyl chain with a double bond at position 3 |
| Molecular formula | C221H366N72O67S |
| Molecular weight | 5,135.9 Da, free base (FDA label); 5,136 g/mol (PubChem) |
| Salt form in the approved product | Acetate |
| CAS number | 218949-48-5 |
| PubChem CID | 16137828 |
| Development code | TH9507 |
| Brand names | Egrifta, Egrifta SV, Egrifta WR |
The FDA label describes tesamorelin as the 44 amino acid sequence of human GRF with a hexenoyl moiety, a C6 chain with a double bond at position 3, attached to the tyrosine residue at the N-terminal part of the molecule. PubChem's systematic name identifies the double bond as E, which is the "trans" in trans-3-hexenoyl.
Apart from that cap, every residue matches native human GHRH. Tesamorelin keeps the lone methionine at position 27 and the Asn8-Ser9 pair, both of which matter for handling (see below).
Why the hexenoyl cap works
DPP-4 cleaves a dipeptide from the free N-terminal amine of a peptide when the second residue is alanine or proline. GHRH, with Tyr1-Ala2 at its N-terminus, is a textbook substrate. Tesamorelin's hexenoyl group is attached to that N-terminal amine as an amide, so the enzyme no longer finds the free amine it needs.
Ferdinandi and colleagues reported three consequences in their 2007 nonclinical paper:
- TH9507 was resistant to dipeptidyl aminopeptidase-IV deactivation.
- Compared with natural hGRF(1-44)NH2, it degraded more slowly in vitro in rat, dog and human plasma.
- Its elimination from plasma in animals was prolonged relative to the native peptide.
The approach differs from the other common GHRH analogs, which change the peptide chain itself.
Tesamorelin compared with other GHRH analogs
| Feature | Sermorelin | CJC-1295 (no DAC) | CJC-1295 (with DAC) | Tesamorelin |
|---|---|---|---|---|
| GHRH residues | 1–29 | 1–29 | 1–29, plus Lys30 | 1–44 |
| Sequence changes | None | D-Ala2, Gln8, Ala15, Leu27 | D-Ala2, Gln8, Ala15, Leu27 | None |
| Added groups | None | None | Maleimidopropionyl on Lys30 | trans-3-hexenoyl on Tyr1 |
| How DPP-4 is addressed | Not addressed | D-Ala at position 2 | D-Ala at position 2, plus albumin conjugation | N-terminal acyl cap |
| Molecular weight (approx.) | 3,358 | 3,368 | 3,647 | 5,136 |
| FDA status | Formerly approved (Geref), withdrawn 2009 | Never approved | Never approved | Approved (Egrifta) |
Sermorelin and both forms of CJC-1295 are covered in Sermorelin vs Ipamorelin and CJC-1295 vs Ipamorelin. The difference that stands out is length. Spiess and colleagues showed in 1982 that GRF(1-29)-NH2 is as active in vitro as the longer forms, which is why most analogs stop at residue 29. Tesamorelin keeps residues 30 to 44 and changes nothing in the chain.
Receptor and signaling
Tesamorelin acts on the GHRH receptor (UniProt Q02643), a 423-residue class B GPCR expressed on somatotroph cells of the anterior pituitary. UniProt describes it as coupled to G proteins that activate adenylyl cyclase, which raises cyclic AMP in the cell and stimulates growth hormone gene transcription and secretion.
The FDA label states that, in vitro, tesamorelin binds and stimulates human GRF receptors with similar potency to endogenous GRF. In other words, the hexenoyl cap changes the peptide's stability, not its receptor pharmacology. The label also describes the downstream sequence: GHRH acts on somatotrophs to stimulate synthesis and pulsatile release of growth hormone, and some of growth hormone's actions are mediated by IGF-1. Our profile of IGF-1 LR3 covers the IGF-1 receptor end of that axis.
Research models
The published nonclinical work on tesamorelin, summarized by Ferdinandi and colleagues, used several species:
- In vitro plasma stability in rat, dog and human plasma, compared directly with native hGRF(1-44)NH2.
- Pharmacodynamic studies in pigs, rats and dogs, measuring plasma growth hormone and IGF-1.
- Subchronic toxicology in rats and dogs for up to four months, with toxicokinetics.
These are the standard components of a nonclinical package for a peptide drug candidate. For in-vitro work today, tesamorelin serves as a DPP-4-resistant, full-length GHRH receptor agonist, which makes it a useful comparator against native GHRH, sermorelin and the CJC-1295 forms in receptor and stability assays.
Regulatory status
Tesamorelin is FDA-approved. The FDA approved it in 2010 as Egrifta, and the current Theratechnologies labels on DailyMed cover Egrifta SV and Egrifta WR. The label's indication is the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy. It is not approved for any other use.
That approval applies to Theratechnologies' finished product. Tesamorelin sold as a research chemical, including by Anhydrolabs, is a laboratory reagent: not for human or veterinary diagnosis, treatment, or consumption. Our research-use page sets out the terms of supply.
What to look for on a certificate of analysis
Because tesamorelin differs from native GHRH only by its cap, the most informative checks are the ones that confirm the cap is present and the chain is intact. A certificate for a research lot should show, at minimum, an HPLC purity figure and an observed mass that matches the expected value within the instrument's tolerance.
| Species | Mass relative to tesamorelin | What it indicates |
|---|---|---|
| Tesamorelin (free base) | 5,135.9 Da | The intended molecule |
| Uncapped GHRH(1-44)-NH2 | About 96 Da lighter | Missing hexenoyl group |
| Met27 sulfoxide | About 16 Da heavier | Oxidation |
| Deamidated form | About 1 Da heavier | Asn converted to Asp or isoAsp |
The hexenoyl group adds C6H8O, about 96.1 Da, to the chain, and PubChem's formula for tesamorelin minus that fragment gives the mass of native GHRH(1-44) amide, about 5,039.8 Da. An observed mass near that lower value would point to uncapped GHRH, which DPP-4 can cleave. Our guides on how to read a peptide certificate of analysis and peptide purity explain how the mass and HPLC entries are generated and what they can and cannot show.
Handling tesamorelin in the lab
At 44 residues and about 5.1 kDa, tesamorelin is one of the larger linear peptides in a typical research catalog. A few features of its sequence are worth knowing before making a stock solution.
- Methionine 27. Methionine oxidizes to methionine sulfoxide, which appears as a +16 Da species by mass spectrometry. Minimizing air exposure, avoiding oxidizing contaminants and keeping solutions cold all reduce it.
- Asparagine 8. An asparagine followed by serine is a sequence motif prone to deamidation in solution, especially at neutral to basic pH and higher temperatures. Deamidation adds about 1 Da and often shows up as a closely eluting species by HPLC.
- Salt form. The approved product is an acetate salt, and its label distinguishes the mass of tesamorelin free base from the mass of tesamorelin acetate. The same distinction applies to research material: the mass on a vial includes counterions, which is worth accounting for when calculating molar concentrations.
- Storage. As a lyophilized powder it is far more stable than in solution. Our post on how long peptides last covers the degradation routes, and the storage and handling page lists the temperatures we use.
Research-grade peptides of this length are generally made by solid-phase synthesis, where an N-terminal acyl group can be coupled on the resin much like one more residue. Our explainer on how peptides are made describes that process.
Anhydrolabs supplies tesamorelin as a lyophilized powder in vacuum-sealed vials, and also as 10-vial kits. The catalog also lists a two-component lyophilized blend, Tesamorelin / Ipamorelin, which pairs a GHRH receptor agonist with a ghrelin receptor agonist.
