Hunger-receptor research peptide (CHEMBL2163483)
A lab-only peptide that binds the hunger receptor in the stomach; used only as a research tool.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
This card represents CHEMBL2163483, a six-residue research peptide reported by Proulx and colleagues (2012) in a structure-activity study of GHRP-6 analogs. It is not a drug, not a supplement, and has no clinical or self-administration use case — it is a single datapoint from a medicinal-chemistry paper, indexed here because it has a measured binding affinity at the ghrelin receptor (GHS-R1a). The full chemical structure is the hexapeptide His-D-Trp-Ala-D-Tyr-D-Phe-Lys-NH₂ (compound 14 in the original paper), with three D-amino acids and a C-terminal amide; the stored 3-letter sequence "HAK" is a placeholder for the standard-letter residues only (His, Ala, Lys) and does not capture the D-stereochemistry, the D-Tyr⁴ substitution, the D-Phe⁵, or the amide cap. The chemistry context is GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂) — the classical synthetic growth hormone secretagogue — with a single Trp⁴ → D-Tyr⁴ substitution.
History
GHRP-6 was developed in the 1980s by Cyril Bowers and collaborators as one of the first synthetic peptides shown to release growth hormone through a then-unknown receptor; that receptor was cloned by a Merck team in 1996 and was later identified as the ghrelin receptor (GHS-R1a) when Kojima and Kangawa isolated ghrelin from rat stomach in 1999. GHRP-6 turned out to have dual affinity — high (nanomolar) at GHS-R1a and lower (micromolar) at the CD36 scavenger receptor, which is implicated in atherosclerosis and angiogenesis. The Proulx group at the Université de Montréal (Proulx et al. 2012, J. Med. Chem.) ran an aza-amino-acid and alanine scan of GHRP-6 to find analogs that kept CD36 affinity while losing GHS-R1a affinity — a selectivity-switch project aimed at probing CD36 biology without confounding GH release. CHEMBL2163483 (compound 14 in that paper) is one of the comparison non-aza analogs in the series.
What it does
In a competition binding assay against radiolabeled ghrelin on GHS-R1a-transfected cell membranes, this peptide bound the ghrelin receptor with an IC50 of 3.25 × 10⁻⁶ M (3250 nM) — roughly 500-fold weaker than GHRP-6 itself (IC50 6.08 × 10⁻⁹ M = 6 nM) at the same receptor (Proulx 2012). It also bound the CD36 receptor in a parallel covalent competition assay with IC50 = 1.20 × 10⁻⁵ M (12 µM), comparable to GHRP-6's CD36 affinity. The substitution of D-Tyr at position 4 (replacing the Trp of GHRP-6) is what produced this 500-fold drop in GHS-R1a affinity while leaving CD36 binding largely intact. No downstream functional assays (GH release, food intake, angiogenesis) are reported for this specific compound in the paper.
Mechanism
GHS-R1a is a Gq-coupled receptor expressed in the pituitary, hypothalamus, and vagal afferents; activation drives PLC/IP3/DAG signaling and, in pituitary somatotrophs, releases growth hormone. The native ligand is octanoylated ghrelin (28 aa); GHRP-6 and its analogs are short peptidomimetics that occupy the same orthosteric pocket. Substituting an aromatic D-amino acid at position 4 of the GHRP-6 backbone disrupts the GHS-R1a binding geometry (CHEMBL2163483 loses ~500-fold affinity) more than it disrupts CD36 binding, supporting the Proulx group's broader thesis that the GHS-R1a and CD36 binding pockets recognize different conformations of the GHRP-6 family.
Evidence
- Human: None. This compound has not been administered to humans.
- Animal: None reported for this specific compound. Other analogs in the same paper were tested in a mouse choroidal explant angiogenesis assay; CHEMBL2163483 was not among them.
- In vitro: GHS-R1a competition binding (rat pituitary / GHS-R1a-transfected cell membranes), IC50 3.25 µM; CD36 covalent competition binding (rat cardiac membranes), IC50 12 µM (Proulx 2012).
Regulatory status
- US: Not an approved drug. Research chemical only. No FDA or DEA classification specific to this compound.
- EU / international: Not an approved drug anywhere.
- WADA: Synthetic ghrelin-receptor agonists are prohibited under WADA's S2 class (peptide hormones, growth factors, related substances and mimetics). This specific compound is not separately listed but falls within the class.
Related peptides
- Ghrelin — the endogenous 28-residue ligand of GHS-R1a that this entire compound family was designed to mimic.
- GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂) — the parent hexapeptide; CHEMBL2163483 differs by a single Trp⁴ → D-Tyr⁴ swap.
- Hexarelin, GHRP-2, ipamorelin, MK-677 (ibutamoren) — other synthetic GHS-R1a agonists in the broader GHRP / growth-hormone-secretagogue family.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| IC50 | 3250 nM | GPCRDB/ChEMBL |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.664 | global PDE — lower = better |
| disorder | NaN | fraction disordered |
▸3-letter notation
▸recipeboltz-2 1.0
| parameter | value |
|---|---|
| model | boltz-2 1.0 |
| weights | — |
| hardware | nvidia_nim_api |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | none |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
▸citationbibtex
@peptide{pep10343,
sequence = {HAK},
target = {ghsr},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}