GHRP-4
GHRP-4 is a synthetic hexapeptide analog in the growth hormone releasing peptide series, acting as a ghrelin receptor agonist with limited published characterization compared to GHRP-2 and GHRP-6.
GHRP-4 is a synthetic hexapeptide growth hormone secretagogue belonging to the family of growth hormone releasing peptides developed through systematic structure-activity relationship studies of the GHS-R1a receptor. As part of the GHRP series pioneered by Cyril Bowers, GHRP-4 represents one of several analogs generated during the optimization of hexapeptide sequences for growth hormone release.
Overview
GHRP-4 emerged from the extensive structure-activity relationship (SAR) studies conducted on hexapeptide growth hormone secretagogues during the 1980s and 1990s. The GHRP family -- including GHRP-1, GHRP-2, GHRP-4, GHRP-5, GHRP-6, and others -- was developed through systematic modification of the hexapeptide backbone to optimize GH releasing potency, selectivity, and pharmacokinetic properties. GHRP-4 occupies a position in this series where limited published data prevents definitive characterization of its pharmacological profile relative to the more extensively studied GHRP-2 and GHRP-6.
Mechanism of Action
As a member of the GHRP hexapeptide family, GHRP-4 is expected to act through the growth hormone secretagogue receptor type 1a (GHS-R1a), a G protein-coupled receptor on pituitary somatotrophs. Activation of GHS-R1a triggers phospholipase C-mediated intracellular calcium release, leading to growth hormone vesicle exocytosis. This pathway operates independently of the GHRH receptor, allowing for synergistic GH release when GHRPs are combined with GHRH analogs. The specific binding affinity and efficacy of GHRP-4 at GHS-R1a relative to other family members has not been extensively reported in peer-reviewed literature.
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GHRP-4
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Research
Growth Hormone Release
Based on its position within the GHRP hexapeptide family, GHRP-4 is expected to stimulate growth hormone release through GHS-R1a agonism. The magnitude and selectivity of this response -- including the degree of associated cortisol and prolactin elevation -- have not been systematically compared to GHRP-2 or GHRP-6 in published studies. The lack of comparative data reflects the rapid convergence of research focus onto GHRP-2 and GHRP-6 once those analogs demonstrated superior pharmacological properties.
Limited Published Data
It is important to note that GHRP-4 has minimal representation in the peer-reviewed literature. Most references to GHRP-4 appear in the context of broad GHRP family reviews or patent filings rather than dedicated pharmacological characterization. Researchers interested in hexapeptide growth hormone secretagogues are generally directed to the extensive literature on GHRP-2 and GHRP-6, which offer well-characterized dose-response profiles, clinical trial data, and established safety records.
Structure-Activity Relationship Context
The GHRP series was developed through iterative modifications of the His-DTrp-Ala-Trp-DPhe-Lys hexapeptide scaffold first identified by Bowers. Each numbered GHRP variant incorporates specific amino acid substitutions designed to alter potency, selectivity, metabolic stability, or side-effect profile. GHRP-2 (D-Ala-D-2Nal-Ala-Trp-D-Phe-Lys) and GHRP-6 (His-DTrp-Ala-Trp-DPhe-Lys) emerged as the most potent and best-characterized members, while intermediate analogs like GHRP-4 received less focused investigation (Bowers, 1998).
Safety Profile
No dedicated safety studies for GHRP-4 have been published. Based on its membership in the hexapeptide GHRP family, expected effects include dose-dependent GH release with potential cortisol and prolactin elevation at higher doses, transient appetite stimulation via GHS-R1a hypothalamic signaling, and mild water retention. The safety profiles of GHRP-2 and GHRP-6, which share the hexapeptide scaffold, provide the closest available reference. No serious adverse effects have been attributed to GHRP-class hexapeptides at standard research doses, though long-term human data for GHRP-4 specifically does not exist.
Clinical Research Protocols
GHRP-4 has not been the subject of formal clinical trials or standardized research protocols. No entries for GHRP-4 appear on ClinicalTrials.gov. For researchers interested in hexapeptide GH secretagogues, established protocols exist for GHRP-2 (the pralmorelin provocation test, approved in Japan for GH deficiency diagnosis) and GHRP-6 (used in various investigational GH stimulation protocols). These protocols typically involve IV or SC administration at 1 mcg/kg with serial GH sampling at 15-minute intervals.
Synergies & Combinations
No combination studies specific to GHRP-4 have been published. However, the synergistic interaction between GHRPs and GHRH analogs is a class-wide phenomenon arising from the distinct receptor mechanisms (GHS-R1a vs. GHRH receptor). GHRP-4 would be expected to demonstrate this synergy based on its shared mechanism of action. In practice, GHRP-2 and ipamorelin are the preferred GHRP partners for GHRH analog combination protocols due to their well-characterized pharmacology.
Pharmacokinetic Profile
GHRP-4 — Pharmacokinetic Curve
Subcutaneous injection, IntravenousQuick Start
- Route
- Subcutaneous injection, Intravenous
Molecular Structure
- Formula
- C34H37N7O4
- Weight
- 607.7 Da
- CAS
- Not widely catalogued
- PubChem CID
- 45157721
- Exact Mass
- 607.2907 Da
- LogP
- 2.1
- TPSA
- 188 Ų
- H-Bond Donors
- 7
- H-Bond Acceptors
- 5
- Rotatable Bonds
- 13
- Complexity
- 1040
Identifiers (SMILES, InChI)
InChI=1S/C34H37N7O4/c1-20(39-33(44)26(35)16-22-18-37-27-13-7-5-11-24(22)27)32(43)41-30(17-23-19-38-28-14-8-6-12-25(23)28)34(45)40-29(31(36)42)15-21-9-3-2-4-10-21/h2-14,18-20,26,29-30,37-38H,15-17,35H2,1H3,(H2,36,42)(H,39,44)(H,40,45)(H,41,43)
UGYIWLNWSAOAAA-UHFFFAOYSA-NResearch Protocols
subcutaneous Injection
Administered via subcutaneous injection.
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| General Research Protocol | 1 mcg | Per protocol | — |
intravenous Injection
Administered via intravenous injection.
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| General Research Protocol | 1 mcg | Per protocol | — |
What to Expect
What to Expect
Rapid onset expected; half-life of Estimated 15-30 minutes (based on GHRP class) indicates fast-acting pharmacokinetics
These protocols typically involve IV or SC administration at 1 mcg/kg with serial GH sampling at 15-minute intervals.
Due to short half-life (Estimated 15-30 minutes (based on GHRP class)), effects are expected per-dose; consistent daily administration maintains...
Regular administration schedule required; effects are dose-dependent and do not persist between doses
Quality Indicators
Red flags
- Significant side effect risk noted
Frequently Asked Questions
References (5)
- [5]
- [6]Davenport et al -- International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function Pharmacol Rev (2005)
- [1]Bowers CY *Cell Mol Life Sci* Cell Mol Life Sci (1998)
- [3]Davenport et al *Pharmacol Rev* Pharmacol Rev (2005)
- [4]Bowers CY et al *Endocrinology* Endocrinology (1994)
GHRP-2
GHRP-2 (pralmorelin) is a synthetic growth hormone secretagogue that binds the ghrelin receptor, with research applications in muscle preservation, appetite regulation, immune function, sleep quality, and pain modulation.
GHRP-6
GHRP-6 is a synthetic ghrelin receptor agonist and growth hormone secretagogue with research applications in neuroprotection, memory, wound healing, cardiac protection, and mood regulation.