pe
pep-10373 v1 CC-BY-SA-4.0

Hormone-signaling research peptide (CHEMBL3085508)

A lab-made peptide that latches onto a brain receptor controlling sex hormone release; used only as a research tool, not a medicine.

statusbioassayed targetGNRHR length8 aa refs2
status 5 / 5
prediction metrics boltz-2 2.2.1
ipTM0.918
pTM0.900
avg pLDDT78.1
ranking score0.808
STRUCTURE · PEP-10373 × GNRHR
ranking0.808
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 2.2.1 · mmCIF ↓ download
sequence8 aa
158
HWSYGLRG
in the news 1 article
overview readme

What this is

This card describes a short research peptide (sequence HWSYGLRG, 8 residues) catalogued in the ChEMBL bioactivity database under the identifier CHEMBL3085508. It is a literature-extracted ligand for the gonadotropin-releasing hormone receptor (GnRHR) — the same pituitary receptor that endogenous GnRH activates to drive LH and FSH release. The card's stored bioassay value is an IC50 of 0.5 nM at the human GnRH receptor (ChEMBL CHEMBL3085508). This is a medicinal-chemistry research compound, not a marketed drug, and there is no clinical or regulatory program attached to this specific 8-mer.

What it does

The peptide binds the human gonadotropin-releasing hormone receptor (GnRHR), with a reported potency in the sub-nanomolar range (IC50 0.5 nM per the linked ChEMBL record). GnRHR is a Gq-coupled pituitary receptor whose physiologic ligand — the decapeptide GnRH — controls the entire hypothalamic-pituitary-gonadal axis through pulsatile release of LH and FSH. Whether this particular 8-mer acts as an agonist or as an antagonist at the receptor is not specified in the dossier, and the card refs are SAR papers rather than a primary publication for this exact sequence, so the functional direction of the activity is not asserted here.

History

The compound is part of a long line of structure-activity work on short GnRH-derived and GnRH-receptor-targeted peptides that began after Schally and Guillemin's groups isolated and sequenced GnRH in the early 1970s. Two streams of that work are reflected in the card's references. Mező and colleagues (J. Med. Chem., 1997) reported synthesis and structure-antitumor activity relationships for analogs of GnRH-III, a parallel decapeptide form found outside mammals, as part of the broader effort to repurpose GnRH scaffolds for oncology. Betz and colleagues (J. Med. Chem., 2006) mapped overlapping but non-identical binding sites on the human GnRH receptor for different classes of nonpeptide antagonists, helping define the receptor's pharmacophore. The HWSYGLRG sequence sits in that medicinal-chemistry territory — short, GnRH-related, characterised against GnRHR — rather than in the clinical pharmacology of the parent hormone.

Evidence

  • Human: No clinical trials of this specific 8-mer (CHEMBL3085508) are recorded in the dossier. No registered trials on ClinicalTrials.gov are linked to this compound identifier.
  • Animal: None recorded in the dossier for this specific sequence.
  • In vitro: ChEMBL records an IC50 of 0.5 nM at the human gonadotropin-releasing hormone receptor for CHEMBL3085508. Supporting receptor pharmacology comes from the broader GnRHR medicinal-chemistry literature, including the antagonist binding-site mapping of Betz and colleagues (2006) and the SAR analysis of GnRH-III analogs by Mező and colleagues (1997).

Mechanism

GnRHR is a class A G-protein-coupled receptor expressed on pituitary gonadotrophs. Activation by pulsatile endogenous GnRH (every 60–120 minutes physiologically) drives Gq/PLC/IP3/DAG signalling and the synthesis and secretion of LH and FSH; continuous (non-pulsatile) receptor occupancy instead causes receptor internalisation and desensitisation, which is the basis for clinical GnRH agonist drugs used to suppress the axis. The HWSYGLRG peptide is a ligand at this receptor with reported sub-nanomolar in vitro affinity, but the dossier does not specify which signalling outcome — agonism, antagonism, or biased activity — has been measured for this sequence, so no functional claim is made here beyond the binding-level potency in ChEMBL.

Regulatory status

This is a research compound, not an approved medicine. No regulatory programme is recorded in the dossier for the HWSYGLRG sequence (CHEMBL3085508). The parent endogenous hormone GnRH and its decapeptide analog gonadorelin have a long but currently sparse regulatory footprint — historical FDA approvals (Factrel for diagnostic use, Lutrepulse for pulsatile therapy) have been discontinued in the US — but that history applies to the decapeptide, not to this 8-mer.

Related peptides

  • Gonadorelin / GnRH — the endogenous decapeptide whose receptor (GnRHR) this 8-mer targets.
  • Leuprolide-class GnRH agonists and nonpeptide GnRHR antagonists are the broader pharmacological context for any functional follow-up on this sequence.
details expand to inspect
full evidence table1 metrics
metricvaluetool
IC50 0.5 nM GPCRDB/ChEMBL
3-letter notation
His-Trp-Ser-Tyr-Gly-Leu-Arg-Gly
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategycolabfold_local
runtime
predicted by
predicted at2026-05-22
citationbibtex
peptidemodel (2026). Hormone-signaling research peptide (CHEMBL3085508) (pep-10373, v1). PeptideModel. https://peptidemodel.com/card/pep-10373
@peptide{pep10373,
  sequence = {HWSYGLRG},
  target   = {gnrhr},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 2 by signal overlap
clinical trials 0 trials · checked 2026-05-22
0
no registered clinical trials as of 2026-05-22; we'll re-check periodically
references 2 papers
discussion no comments
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