Hunger-receptor binding peptide HAWK (CHEMBL105462)
A tiny four-amino-acid lab probe that binds the same receptor as the hunger hormone ghrelin; used only as a research tool, not a drug.
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
HAWK is a four-residue research peptide (His-Ala-Trp-Lys) catalogued in ChEMBL as CHEMBL105462. It is a binder of the growth hormone secretagogue receptor (GHSR), the same receptor that the natural hunger hormone ghrelin and the synthetic GHRP / growth-hormone secretagogue series (GHRP-6, GHRP-2, hexarelin, ipamorelin) all act through. It is a medicinal-chemistry probe, not a therapeutic — it appears in the public bioactivity literature as a data point on the structure–activity landscape around GHSR, not as a clinical or self-administered compound.
What it does
In vitro, CHEMBL105462 binds GHSR with a reported potency of IC50 = 3.65 nM (ChEMBL CHEMBL105462). GHSR (GHS-R1a) is a Gq-coupled receptor expressed in the pituitary and hypothalamus; the medicinal-chemistry programs that surround this molecule were searching for compact ligands that retain affinity at GHSR while shedding the size and metabolic liabilities of larger peptidic agonists (Nargund 1998, Ankersen 1998). What HAWK does in living systems — agonist vs antagonist behavior, downstream signaling, in vivo activity — is not characterized in the references attached to this card.
History
The GHSR ligand series that CHEMBL105462 belongs to grew out of the late-1990s effort to find small, orally tractable replacements for the early growth hormone-releasing peptides. The receptor itself was identified through a radioligand-tagging approach (Dean 1996) and rapidly became the target of several parallel chemistry programs at Merck, Novo Nordisk, and others, producing both peptidic scaffolds (Ankersen 1998, Hansen 1998) and non-peptide leads such as the 3-spiropiperidines (Yang 1998) and quinazolinones (Ye 2000). These efforts laid the design groundwork for the clinically advanced GHSR agonists that came later, including the diagnostic macimorelin and the cancer-cachexia agent anamorelin. HAWK / CHEMBL105462 sits inside this exploratory landscape as a compact tetrapeptide data point rather than a clinical lead.
Evidence
- In vitro: IC50 = 3.65 nM at GHSR (ChEMBL CHEMBL105462). No additional functional or selectivity data is attached to this card.
- Animal: None attached.
- Human: None. This compound has not entered clinical investigation.
Mechanism
GHSR (GHS-R1a) is a Gq-coupled GPCR that, when activated by ghrelin or by synthetic agonists, signals via PLC / IP3 / DAG with downstream calcium mobilization. In pituitary somatotrophs this drives growth hormone release; in the hypothalamic arcuate nucleus, GHSR activation on NPY/AgRP neurons drives appetite. Peptidomimetic programs around this receptor (Nargund 1998, Proulx 2012) have specifically aimed to identify scaffolds that retain GHSR engagement while being small, orally absorbable, and selective against related receptors such as CD36, which shares ligand overlap with the GHRP series (Proulx 2012). Whether CHEMBL105462 is a full agonist, partial agonist, or antagonist at GHSR is not specified in the references attached to this card — only its binding potency is reported.
Related peptides
- Ghrelin — the endogenous 28-residue ligand of GHSR; the reference biology for the entire growth hormone secretagogue field.
- GHRP-6, GHRP-2, hexarelin, ipamorelin — the classical synthetic peptide agonists of the same receptor, which the small-ligand programs around CHEMBL105462 were trying to improve on in terms of size and oral bioavailability.
Open questions
- Functional pharmacology at GHSR — agonist, antagonist, or biased? Not characterized in the attached references.
- Selectivity against CD36 and other ghrelin-adjacent receptors — unknown.
- In vivo behavior of any kind (PK, GH release, appetite, plasma stability) — not reported in the attached references.
- Whether this tetrapeptide was ever advanced beyond the initial binding screen or remained a single ChEMBL data point.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| IC50 | 3.65 nM | GPCRDB/ChEMBL |
▸3-letter notation
▸recipeboltz-2 2.2.1
| parameter | value |
|---|---|
| model | boltz-2 2.2.1 |
| weights | — |
| hardware | vast_v100_32gb |
| mlx version | — |
| python | — |
| random seed | 1 |
| msa strategy | colabfold_local |
| runtime | — |
| predicted by | — |
| predicted at | 2026-05-22 |
▸citationbibtex
@peptide{pep10341,
sequence = {HAWK},
target = {ghsr},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}