Tesamorelin

At a glance

Strengths

5 mg and 10 mg

Also known as

TH9507; TH-9507; (3E)-hex-3-enoyl-somatoliberin; tesamorelin acetate (salt form)

CAS number

218949-48-5

Molecular formula

C221H366N72O67S

Molecular weight

5136 g/mol (free base; FDA label: 5135.9 Da)

Sequence

(E)-hex-3-enoyl-YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL-NH2 (44 residues)

PubChem CID

16137828

What tesamorelin is

Tesamorelin is the complete 44-residue sequence of human GHRH, with one chemical change at the N-terminus. The native hormone is also called growth hormone-releasing factor (GRF) or somatoliberin. Theratechnologies developed tesamorelin under the code TH9507. Its nonclinical characterisation was published in 2007 ¹. The authors reported that adding a trans-3-hexenoyl group to Tyr1 made the peptide resistant to deactivation by dipeptidyl aminopeptidase-IV. Compared with the native peptide, it also degraded more slowly in rat, dog and human plasma in vitro ¹. This stability is the main structural difference from native GHRH, whose amino acid sequence tesamorelin keeps unchanged. Tesamorelin should not be confused with sermorelin or CJC-1295. Those are separate synthetic GHRH analogs with their own structures and their own analytical reference data ².

Chemical identity

The sequence is (E)-hex-3-enoyl-YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL-NH2. It has one methionine, at position 27, and ends in leucinamide. PubChem lists tesamorelin as CID 16137828, with the formula C221H366N72O67S and a molecular weight of 5136 g/mol. The FDA label gives 5135.9 Da as the free base equivalent and describes the approved substance as an acetate salt. The CAS number for the free peptide is 218949-48-5. PubChem also records two deprecated CAS numbers, 804475-66-9 and 775305-79-8, which still appear in older documents. FDA's substance registry lists 901758-09-6 for tesamorelin acetate. Because it has more than 40 amino acids, FDA treats tesamorelin as a protein rather than a peptide, even though it is made by chemical synthesis.

Regulatory status

FDA approved tesamorelin as Egrifta, sponsored by Theratechnologies, on November 10, 2010, under application 022505. On March 23, 2020, under the Biologics Price Competition and Innovation Act, that approval was deemed a biologics license, now BLA 022505. FDA's published list of transitioned products names tesamorelin acetate (Egrifta and Egrifta SV). The current FDA labels, for Egrifta SV and Egrifta WR, set out the approved indication; they are available through Drugs@FDA. GHRH and its synthetic analogs are also prohibited in sport by the World Anti-Doping Agency ²³. The tesamorelin sold here is not Egrifta. It is not covered by any FDA license, FDA has not assessed it, and it is intended for laboratory research only, not for administration to humans or animals.

Published research

The literature divides into the developer's programme and later analytical work.

• Nonclinical pharmacology (2007). Plasma stability in vitro and the nonclinical safety evaluation of TH9507 ¹.
• Development programme (reviewed 2009). A review of tesamorelin's development describes a multicentre, randomised, placebo-controlled phase 3 trial ⁴.
• Drug interaction study (2013). Two randomised, two-way crossover studies in healthy volunteers investigated the potential impact of tesamorelin on CYP3A activity by examining its effect on the pharmacokinetics of simvastatin and ritonavir ⁵.
• Anti-doping analysis (2016 and 2021). An immunoaffinity method with high-resolution mass spectrometry for four GHRH analogs in human plasma ³, and a study of in vitro metabolism with a liquid chromatography-tandem mass spectrometry method for detection in urine ².

What is not known

The FDA label states that the long-term cardiovascular safety of the approved medicine has not been established. The approved medicines contain the inactive ingredients listed on their labels, which research material may not contain. Stability data for the medicines therefore cannot be assumed to apply to research powder. For research tesamorelin powder, the solid-state degradation products remain undescribed in the peer-reviewed literature. In vitro metabolites have been characterised for anti-doping purposes ², but that work does not address storage of the solid.

Laboratory storage and handling

Store research tesamorelin as stated on the lot's certificate of analysis and product label. The Egrifta SV label allows controlled room temperature with protection from light, but that permission belongs to a formulated medicine and should not be read across to unformulated powder. Methionine 27 is the residue most likely to oxidise, so time with the vial open to air should be short. Moisture is the second concern: the vial should be at room temperature before it is opened, so that no condensation forms on the powder.

Quality testing

Identity on the certificate of analysis should rest on mass spectrometry: the free peptide's mass is about 5136 Da. That check also separates tesamorelin from unmodified GHRH(1-44) amide, which lacks the hexenoyl group and is about 96 Da lighter. A methionine-oxidised form appears 16 Da heavier. For purity, reversed-phase HPLC is the expected method, ideally reported with its chromatogram. Acetate content, together with water and peptide content, shows how much of a weighed amount is tesamorelin itself. A liquid chromatography-tandem mass spectrometry method for tesamorelin and its in vitro metabolites in urine has been published for anti-doping work ², and an immunoaffinity method detects it in plasma ³.