GHRP-2 Acetate

GHRP-2 Acetate (Growth Hormone Releasing Peptide-2, Pralmorelin, D-Ala-D-beta-Naphthylalanine-Ala-Trp-D-Phe-Lys-NH2) is a second-generation synthetic hexapeptide GHS-R1a agonist developed through structure-activity optimisation of the first-generation GHRP-6. The substitution of D-beta-Naphthylalanine at position 2 (replacing GHRP-6's D-Trp2) achieves higher GHS-R1a affinity, while the D-Ala1 substitution (replacing His1) reduces off-target receptor activities. GHRP-2 was developed as Pralmorelin and progressed to Phase 2 clinical trials as a GH stimulation test agent, generating published human pharmacokinetic and pharmacodynamic reference data.

GHS-R1a (the ghrelin receptor) is a class A GPCR that couples to Gq/11, activating phospholipase C-beta upon agonist binding. PLCbeta cleaves PIP2 into IP3 (triggering calcium release from the ER in pituitary somatotrophs) and DAG (activating PKC). The calcium transient generated by IP3/IP3R activity is the primary driver of GH secretory granule exocytosis — SNARE protein-dependent membrane fusion with the plasma membrane releases GH into the portal circulation. Published GHS-R1a pharmacology using GHRP-2 has characterised receptor binding kinetics (Ki in the low nanomolar range), GH secretion kinetics (peak GH at 15-30 minutes, return to baseline by 90-120 minutes in human and rodent studies), and receptor selectivity relative to earlier GHRPs.

The pharmacological distinction between GHRP-2 and Ipamorelin is receptor selectivity. GHRP-2 at supramaximal concentrations produces measurable ACTH elevation and cortisol stimulation through off-target receptor activation (proposed to involve CRF receptors or direct pituitary corticotroph stimulation). Ipamorelin at equivalent GH-releasing concentrations produces no detectable ACTH or cortisol changes. This selectivity difference is both a limitation and a research tool: for studies requiring isolated GHS-R1a pharmacology without HPA axis involvement, Ipamorelin is preferred; for studies examining the relationship between GHS-R1a activation and HPA axis biology — as a pharmacological model of ghrelin's stress response connections — GHRP-2 is the appropriate comparative tool.

GHRP-2's appetite-stimulating activity through hypothalamic NPY/AgRP neuron GHS-R1a activation is intermediate between the strong orexigenic GHRP-6 and the minimal appetite effect of Ipamorelin. This graduated appetite-stimulating series (GHRP-6 > GHRP-2 > Ipamorelin) enables systematic research into the structural determinants of appetite activity within the GHRP pharmacophore — what differences in the hexapeptide sequence drive the orexigenic versus non-orexigenic profile.

Clinical pharmacokinetic data from Pralmorelin development: subcutaneous bioavailability approximately 70-80%; Tmax approximately 30 minutes; rapid clearance (half-life approximately 15-20 minutes) due to peptidase degradation of the L-amino acid residues; GH peak at 15-30 minutes in human subjects. This published clinical dataset contextualises laboratory research concentrations and incubation time selection.

Research applications include: GHS-R1a binding assays (radioligand displacement with [125I]-ghrelin or [35S]-GTPgammaS functional assays); pituitary somatotroph GH secretion studies (primary rat pituitary cells, GH3 cells); comparative selectivity profiling alongside GHRP-6 and Ipamorelin across GH, ACTH, and prolactin secretion endpoints; and appetite circuit research in hypothalamic NPY/AgRP neuron models examining GHS-R1a-mediated NPY release and AgRP expression.

MW: 817.94 g/mol. CAS: 158861-67-7. Molecular formula: C45H55N9O6. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.

For comparative research alongside Ipamorelin and GHRP-6: prepare all three compounds at matched molar concentrations (not mass concentrations — molecular weights differ: GHRP-2 MW 817.94, GHRP-6 MW 873.03, Ipamorelin MW 711.85). Measure GH, ACTH, prolactin, and cortisol in parallel from the same pituitary cell preparation to directly compare selectivity ratios. GHRP-2's intermediate profile (higher selectivity than GHRP-6, lower than Ipamorelin) makes it the pivotal comparison point for characterising structure-selectivity relationships across the GHRP series. MW: 817.94 g/mol. CAS: 158861-67-7. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.