Tesamorelin

Tesamorelin is a synthetic analogue of full-length human GHRH(1-44) incorporating an N-terminal trans-3-hexenoic acid modification that provides DPP-IV resistance while preserving the authentic 44 amino acid GHRH sequence. Approved by the FDA as Egrifta for HIV-associated lipodystrophy, Tesamorelin is the only clinically approved full-length GHRH analogue and provides the most extensively characterised published pharmacology dataset of any GHRH research tool compound.

Endogenous GHRH is a 44 amino acid peptide. While research established that GHRH(1-29) (Sermorelin) contains the complete GHRHR-activating pharmacophore, the full-length GHRH(1-44) retains the authentic C-terminal 15 residues (positions 30-44) that contribute to: additional GHRHR extracellular domain contacts (improving binding affinity compared to 1-29 fragments); an extended alpha-helical structure that may stabilise the N-terminal receptor-activating helix; and potential interactions with heparan sulphate proteoglycans on cell surfaces through basic residues in the C-terminal extension.

The N-terminal trans-3-hexenoic acid modification blocks the DPP-IV cleavage site at the Tyr1-Ala2 bond (note: Tesamorelin's native sequence begins with Tyr-Ala, and the hexenoic acid caps the N-terminus) — the same cleavage site targeted by DPP-IV in Sermorelin (where Tyr-Ala2-Asp3 is cleaved). This N-terminal cap provides DPP-IV resistance and a plasma half-life of approximately 30 minutes — substantially longer than Sermorelin's 10-20 minutes — while maintaining the complete GHRH(1-44) pharmacophore.

The clinical approval of Tesamorelin for HIV-associated lipodystrophy provides an extensive published dataset. The lipodystrophy syndrome in HIV patients includes visceral adipose tissue (VAT) accumulation, metabolic syndrome features, and elevated cardiovascular risk. Tesamorelin-driven GH axis stimulation selectively reduces VAT in published randomised controlled trials (Falutz et al., NEJM 2007), with primary endpoints of VAT reduction measured by CT scanning. Secondary endpoints included IGF-1 elevation (confirming GH axis stimulation), lipid profile changes, and quality of life measures. The selectivity for VAT over subcutaneous adipose tissue reduction has been attributed to higher GH receptor density and sensitivity in visceral fat depots.

For comparative GH axis research: Tesamorelin provides the full-length GHRH reference; CJC-1295 No DAC provides the stabilised GHRH(1-29) reference; Sermorelin provides the native GHRH(1-29) with DPP-IV sensitivity reference. Systematic comparison of all three in parallel pituitary cell preparations characterises the pharmacological contributions of: full-length sequence (Tesamorelin vs CJC-1295 No DAC), N-terminal cap modification (Tesamorelin vs Sermorelin), and DPP-IV-resistant D-Ala2 modification (CJC-1295 No DAC vs Sermorelin).

GHRHR research endpoints: cAMP accumulation (primary Gs pathway readout) in primary pituitary cells or GHRHR-HEK293 cells; GH secretion ELISA from pituitary cell culture; GH pulse characterisation in rodent in vivo models; IGF-1 production kinetics (4-8 hours post-GH pulse); and GHRHR internalisation kinetics comparing Tesamorelin, CJC-1295 No DAC, and Sermorelin using GHRHR-GFP constructs.

MW: approximately 3357 g/mol (GHRH 1-44 sequence) plus hexenoic acid modification. Reconstitute in bacteriostatic water at 1mg/mL. Contains methionine — store at -20°C away from oxidants. For laboratory and analytical research purposes only.

For comparative GHRH analogue research (Tesamorelin vs CJC-1295 No DAC vs Sermorelin): prepare all three at matched molar concentrations in primary rat anterior pituitary cell culture (correct for MW differences: Tesamorelin approximately 3357, CJC-1295 No DAC 3367.9, Sermorelin 3357.88 g/mol — nearly identical, use 1:1 mass ratio). Incubate for 1, 2, 4, and 8 hours, collecting medium at each timepoint for GH ELISA. Plot GH secretion over time for each compound — Sermorelin shows declining GH release as DPP-IV degrades it; CJC-1295 No DAC and Tesamorelin maintain GH-stimulating activity longer due to DPP-IV resistance. To test full-length sequence contribution (Tesamorelin 1-44 vs CJC-1295 No DAC 1-29): at a concentration producing equivalent initial GH release, extend the assay to 24 hours and compare cumulative GH output — the C-terminal 15 residues of Tesamorelin may contribute sustained GHRHR occupancy through additional ECD contacts. MW: approximately 3357 g/mol plus N-terminal hexenoic acid. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.