Tesamorelin 10mg

Tesamorelin (TH9507) is a synthetic 44-amino acid analog of endogenous GHRH with a molecular weight of 5135.9 Da. It was developed by Theratechnologies Inc. to overcome the inherent instability of native GHRH, which has a half-life of only 3–8 minutes due to rapid cleavage by DPP-4. [1] [2]

Key Structural Feature: A trans-3-hexenoic acid group is anchored to the N-terminal tyrosine (Tyr1), rendering the peptide resistant to DPP-4 degradation and extending the half-life to approximately 26–38 minutes. C-terminal is amidated (-NH₂). [3]

Regulatory Status:

• FDA: Tesamorelin is the active ingredient of an FDA-approved pharmaceutical (Egrifta); that approval does not apply to this research-grade material. [4]
• EMA: Application withdrawn; not marketed in the EU. [6]
• WADA: Prohibited (S2 — Peptide Hormones, Growth Factors). [5]

Developer: Theratechnologies Inc. (Montreal, Canada) — originally designated TH9507.

Pharmacokinetic Highlights:

• Half-Life: ~26–38 min; ~11 min (WR formulation)
• Pulsatility: Preserves natural pulsatile GH secretion (unlike rhGH)

Discovery and design rationale

Theratechnologies developed tesamorelin in the late 1990s by introducing a single trans-3-hexenoyl modification at the N-terminal tyrosine of the native 44-residue GHRH(1-44) sequence. The strategy was deliberately conservative: keep the full-length GHRH backbone so the molecule retains GHRH-receptor selectivity and binding affinity, but block the dipeptidyl-peptidase-4 cleavage site responsible for the <5-minute half-life of native GHRH. The modification yielded a research compound with the same downstream signaling profile as native GHRH but with a circulating duration suitable for animal and clinical investigation models. [1]

Research framework

Within the GHRH-axis and metabolic peptide research family, tesamorelin is most directly compared with sermorelin (truncated GHRH(1-29) analog) and CJC-1295 (long-acting GHRH analog with DAC variant). For visceral-adipose endpoints it is also paired with the lipolytic hGH-fragment analog AOD-9604. These cross-comparisons inform research designs that aim to dissect GHRH-receptor-mediated effects from direct hGH-receptor or beta-3-adrenergic-driven adipocyte responses. [2]

1. Receptor Target — GHRH Receptor

Tesamorelin acts as a specific agonist for the GHRH receptor (GHRHr), a seven-transmembrane G protein-coupled receptor (GPCR) located on somatotroph cells in the anterior pituitary gland. Binding potency is comparable to endogenous GHRH. [7]

2. DPP-4 Resistance

The trans-3-hexenoic acid modification at the N-terminal Tyr1 acts as a chemical shield against DPP-4 cleavage. Native GHRH is rapidly degraded (T½ ~5 min); Tesamorelin's modification extends stability to ~26–38 min. [3]

3. Downstream Signaling Cascade

Gₛ → Adenylyl Cyclase → cAMP → PKA → Ca²⁺ Influx → GH Exocytosis:

1. Receptor activation triggers the Gₛα subunit
2. Gₛα stimulates adenylyl cyclase, converting ATP to cAMP
3. Elevated cAMP activates Protein Kinase A (PKA)
4. PKA opens voltage-gated Ca²⁺ channels → calcium influx
5. Ca²⁺ triggers exocytosis of pre-stored GH vesicles
6. Simultaneously, cAMP promotes GH gene transcription (new GH synthesis) [7]

The product supplied here is for research use only regardless of regulatory status of related formulations.

4. Selectivity

Tesamorelin is highly selective for the GHRH receptor. It does not significantly alter TSH, LH, ACTH, or Prolactin levels. Unlike GHRPs (e.g., Ipamorelin), it does not bind the ghrelin receptor. [9]

5. Receptor-Level Summary

Receptor-level: GHRH-receptor agonist at anterior-pituitary somatotrophs (cAMP/PKA signalling).

6. Comparison with Related Molecules

7. Pharmacokinetics

Regulatory Context

Tesamorelin is the active ingredient of an FDA-approved pharmaceutical (Egrifta). That approval does not apply to this research-grade material. Published literature is listed under References.

GHRH-Receptor Pulsatility Profiling

Tesamorelin is used as a research tool to investigate whether stimulating endogenous, pulsatile GH secretion through the GHRH-receptor produces a different downstream IGF-1 and metabolic-substrate signature compared with continuous exogenous recombinant human GH. Pharmacokinetic-pharmacodynamic studies in healthy volunteer cohorts have catalogued amplitude, frequency, and trough patterns that inform research models of natural-pulsatility versus tonic-elevation GH biology. [7]

Comparative Research Context

Within the GHRH-axis research family, tesamorelin is most directly compared with sermorelin (truncated GHRH(1-29)), CJC-1295 (long-acting GHRH analog), and the lipolytic hGH-fragment AOD-9604. These cross-comparisons help research teams dissect GHRH-receptor-mediated visceral-adiposity effects from direct hGH-receptor or beta-3-adrenergic-driven adipocyte responses.

Clinical Trials

Handling Safety

Handle with standard laboratory PPE. Consult the SDS.