Key findings
- Adding a trans-3-hexenoyl moiety to Tyr1 of the 1-44 amide made the analogue resistant to dipeptidyl aminopeptidase IV and slowed its in-vitro degradation in rat, dog and human plasma. [1]
- Enzyme kinetics on the parent hormone placed the dipeptidyl peptidase IV cleavage between Ala2 and Asp3, the bond the N-terminal modification is built to protect. [2]
- A validated immunopurification and high resolution mass spectrometry method reached a limit of detection of 0.2 ng/mL and a limit of identification of 0.5 ng/mL for the analogue and related growth hormone releasing hormone peptides. [3]
- In-vitro metabolism work on four larger growth hormone releasing hormone analogues identified nineteen major metabolites, which were then synthesized as reference materials for a liquid chromatography tandem mass spectrometry method. [4]
Identity and structure
- Parent sequence
- An analogue of human growth hormone releasing factor 1-44 amide with a trans-3-hexenoyl group added to Tyr1 [1]
- Length
- A 44 amino acid peptide analogue of natural human growth hormone releasing factor [5]
- Distinguishing property
- Resistant to dipeptidyl aminopeptidase IV cleavage, unlike the unmodified 1-44 amide [1]
- Analytical separation
- Listed as a distinct target analyte alongside sermorelin and the two CJC-1295 forms in validated detection methods [4][3]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
The N-terminal modification exists to block the dipeptidyl peptidase IV cleavage that inactivates the native factor. Kinetic work on the parent hormone and its fragments located that cleavage between Ala2 and Asp3 and found comparable initial rates for the 1-44, 1-29 and 1-20 amides, so the liability is carried by the N-terminus rather than by chain length. [2][1]
Analogue design work on the same peptide family showed that the native 1-44 amide is also lost through chemical rearrangement at Asn8 and oxidation at Met27 in aqueous conditions, which is why substitutions at those residues were combined with N-terminal changes. The analogues in that study were 1-32 constructs rather than the 44-residue material. [6]
Research findings
Preclinical in vivo
- System
- Rat, dog and human plasma for in-vitro degradation, alongside repeat-exposure studies in rats, dogs and pigs
- Measured
- In-vitro degradation rate in each plasma, plasma elimination kinetics of the immunoreactive analogue, growth hormone and insulin-like growth factor 1, apparent elimination half-life
- Reported
- The modification slowed in-vitro degradation in rat, dog and human plasma and prolonged plasma elimination. Growth hormone and insulin-like growth factor 1 rose in pigs, rats and dogs on repeated exposure. Apparent elimination half-life in dogs ranged from 21 to 45 min. [1]
Preclinical in vivo
- System
- Male beagle dogs, with timed plasma sampling across three study arms
- Measured
- Plasma concentration of the analogue by radioimmunoassay, relative and absolute bioavailability, terminal half-life, mean residence time
- Reported
- Terminal half-life was 39 min in one arm and 26 min in another, with no significant difference between them. Mean residence time differed between those arms, at 74 min against 52 min. Relative bioavailability between them was 41 percent, with absolute bioavailability estimated at 13 percent. [5]
In vitro
- System
- Purified human placental dipeptidyl peptidase IV with synthetic human growth hormone releasing factor and its fragments, followed by HPLC; the study material is the unmodified parent and its analogs rather than the hexenoyl-modified catalog material
- Measured
- Initial rates of Ala2-Asp3 cleavage, catalytic parameters for P1-substituted analogs
- Reported
- Initial rates were about 5 micromol per min per mg for the 1-44, 1-29 and 1-20 amides. Lower activity for shorter fragments and cyclic lactam analogs indicated S1 prime to Sn prime binding. Peptides with D-configuration at P2, P1 or P1 prime and the desamino-Tyr1 and N-methyl-Tyr1 analogs were not cleaved. [2]
In vitro
- System
- Rat pituitary cell culture and plasma incubations with 1-32 analogues carrying His1, Val2, Thr or Gln8, Ala15 and Leu27 substitutions; these constructs differ from the 44-residue catalog material
- Measured
- Dipeptidyl peptidase IV cleavage over a 24 h incubation, rate of aqueous isomerization, growth hormone releasing activity
- Reported
- The His1 and Val2 substitution completely inhibited dipeptidyl peptidase IV cleavage over 24 h and greatly increased plasma stability. Substitutions at residue 8 slowed isomerization. In rat pituitary cell culture the three analogues were about threefold more potent than the native 1-44 amide. [6]
Analytical
- System
- Fortified urine containing sermorelin, tesamorelin, CJC-1295 and CJC-1295 with drug affinity complex, plus nineteen synthesized in-vitro metabolites as reference materials
- Measured
- Identity of the in-vitro metabolites and limits of detection by liquid chromatography tandem mass spectrometry
- Reported
- Nineteen major in-vitro metabolites were identified across the four analogues, then synthesized, purified and characterized in house. Limits of detection for the target peptides were generally 1 ng/ml or less. [4]
Analytical
- System
- Human urine enriched by magnetic bead immunopurification before liquid chromatography coupled to quadrupole Orbitrap high resolution mass spectrometry
- Measured
- Recovery across bead supports, binding capacities and affinity chemistries; specificity, precision, matrix effect, limit of detection and limit of identification
- Reported
- After selecting the beads with the best recoveries the method was fully validated. Intra-day and inter-day precision were below 15 and 25 percent, the limit of detection was 0.2 ng/mL and the limit of identification 0.5 ng/mL. [3]
Handling for in-vitro work
- Storage
- Lyophilized material kept at minus 20 degrees C, dark and dry; reconstituted aliquots kept cold and used promptly
Open questions
- No cited study reports a growth hormone releasing hormone receptor binding constant for this exact 44-residue construct, so its receptor affinity is inferred from functional work rather than measured here.
- Whether a given vial holds the hexenoyl-modified 44-residue analogue rather than an unmodified fragment is an analytical identity question; the cited detection methods can answer it but none of them was applied to catalog material.
A large clinical literature exists for this analogue and concerns a finished pharmaceutical formulation. It is out of scope for a research material profile and none of it is summarized here.
Lot records
Check the record for the exact material you order. A published paper and a batch certificate answer different questions.
- RV-24-0046-3 ↗Tesamorelin · 99.50% HPLC2026-09-22
- RV-24-0046-2 ↗Tesamorelin · 99.50% HPLC2026-09-22
- RV-24-0046-1 ↗Tesamorelin · 99.50% HPLC2026-09-16
References
- Ferdinandi ES, Brazeau P, High K, et al. Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic & clinical pharmacology & toxicology. 2007.
- Bongers J, Lambros T, Ahmad M, et al. Kinetics of dipeptidyl peptidase IV proteolysis of growth hormone-releasing factor and analogs. Biochimica et biophysica acta. 1992.
- Pont L, Alechaga É, Terrero A, et al. Comparison of magnetic bead surface functionalities for the immunopurification of growth hormone-releasing hormones prior to liquid chromatography-high resolution mass spectrometry. Journal of chromatography. A. 2020.
- Memdouh S, Gavrilović I, Ng K, et al. Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug testing and analysis. 2021.
- Jansen M, Darby I, Abribat T, et al. Pulmonary delivery of TH9507, a growth hormone releasing factor analogue, in the dog. International journal of pharmaceutics. 2004.
- Campbell RM, Stricker P, Miller R, et al. Enhanced stability and potency of novel growth hormone-releasing factor (GRF) analogues derived from rodent and human GRF sequences. Peptides. 1994.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.