Tesamorelin (TH9507): Full-Length GRF With an N-Terminal Cap

Tesamorelin takes the opposite approach to most growth hormone-releasing factor (GRF) analogs. Instead of cutting the hormone down and swapping residues, its developers kept all 44 amino acids of human GRF and added one small chemical group at the front. This Vial Post explainer covers what that group is, why it was put there, how tesamorelin compares with its shorter relatives in stability tests, and what its identity numbers look like.

Nothing here is guidance on use in people or animals. The Vial Post covers tesamorelin only as a subject of laboratory and literature research.

One Addition, No Substitutions

• The parent sequence. Human GRF was first isolated in 1982 as a 44-amino-acid amidated peptide from a human pancreatic tumor (Guillemin 1982).
• The change. The U.S. prescribing information describes tesamorelin as the 44-amino-acid sequence of human GRF with a hexenoyl group, a six-carbon chain with a double bond at position 3, attached to the N-terminal tyrosine (DailyMed: Egrifta WR). Theratechnologies' 2007 nonclinical paper calls it a "minimally modified" analog carrying a trans-3-hexenoyl moiety on Tyr1 (Ferdinandi 2007).
• Development code. PubChem lists TH9507 as a synonym (PubChem: Tesamorelin).

Why Cap the N-Terminus?

Plasma inactivates native GRF mainly through dipeptidylpeptidase IV (DPP-IV), which cuts between residues 2 and 3, with trypsin-like enzymes playing a smaller role (Frohman 1989). Most analogs deal with this by changing residue 2, often to a D-amino acid (Frohman 1989). Tesamorelin leaves the sequence alone and blocks the N-terminus instead.

The 2007 nonclinical study reported that the modification (Ferdinandi 2007):

• made the peptide resistant to DPP-IV deactivation;
• slowed in vitro degradation compared with natural hGRF(1-44)NH2 in rat, dog and human plasma;
• prolonged plasma elimination of immunoreactive TH9507 in vivo, with an apparent elimination half-life of 21 to 45 minutes in dogs;
• raised plasma growth hormone and IGF-1 in pigs, rats and dogs.

How It Compares in a Plasma Test

A 2016 study from the Center for Preventive Doping Research in Cologne put tesamorelin side by side with three shorter GRF peptides (Knoop 2016):

• In human plasma in vitro: no degradation products of considerable abundance were found for tesamorelin, which the authors read as substantial resistance to proteolysis. Sermorelin, hGRF(1-29)NH2, was progressively broken down to GRF(3-29) and had disappeared entirely after 4 hours.
• In rats: tesamorelin was detected in plasma at every sampling point up to 8 hours after intravenous administration.

The authors stress that their results were qualitative and that they made no pharmacokinetic interpretation (Knoop 2016).

What the Label Says About Mechanism

The prescribing information states that in vitro, tesamorelin binds and stimulates human GRF receptors with potency similar to endogenous GRF, and that it stimulates growth hormone secretion, which in turn raises IGF-1 and IGFBP-3 (DailyMed: Egrifta WR). Tesamorelin has held a U.S. approval since 2010; the current label restricts its indication to one defined condition in adults with HIV (DailyMed: Egrifta WR). This article does not discuss that clinical use.

Identity Numbers

• PubChem (free base): C221H366N72O67S, computed molecular weight about 5,136 g/mol (PubChem: Tesamorelin).
• Label: prepared as an acetate salt with about seven acetates per molecule; molecular weight 5135.9 Da as free base equivalent (DailyMed: Egrifta WR).
• Mass spectrometry: monoisotopic mass 5132.7 Da, observed as the 7+ ion at m/z 734 (Knoop 2016).

The gap between the average weight (about 5,136) and the monoisotopic mass (5,132.7) is normal for a peptide this size. A COA should say which kind of mass it reports, and whether the stated weight refers to the free base or the acetate salt.

Frequently Asked Questions

How is tesamorelin different from CJC-1295 without DAC? Tesamorelin keeps all 44 native residues and adds an N-terminal hexenoyl group (DailyMed: Egrifta WR). CJC-1295 without DAC is a 29-residue fragment with four substitutions (Knoop 2016). See our explainer on CJC-1295 without DAC.

Why does the hexenoyl group protect the peptide? DPP-IV removes the first two residues of GRF; the trans-3-hexenoyl group on Tyr1 made TH9507 resistant to that deactivation (Frohman 1989; Ferdinandi 2007).

Why might two documents list slightly different masses? One may give the average molecular weight and the other the monoisotopic mass, and some list the salt form (PubChem: Tesamorelin; DailyMed: Egrifta WR; Knoop 2016). Our explainer on HPLC versus mass spec covers how the tests differ.

For research and educational use only. This article is not medical advice and does not describe dosing or human use.