Blood-vessel-tightening blocker (LDVIW / CHEMBL319660)
A tiny lab-made peptide that blocks a receptor controlling how hard blood vessels squeeze; used only as a lab 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 describes a short peptide — Leu-Asp-Val-Ile-Trp (LDVIW) — catalogued in ChEMBL as a research ligand against the human endothelin A receptor (EDNRA). It is a five-residue research compound, not a drug. It comes from a 1990s medicinal-chemistry programme that took the C-terminal tail of the natural hormone endothelin-1 and used it as a starting point to design small peptide antagonists of the endothelin receptors. Endothelin-1 is one of the most powerful vasoconstrictor signals the body makes, and blocking its receptors is now an established treatment strategy for pulmonary arterial hypertension. LDVIW sits in the SAR (structure–activity relationship) lineage that produced the lead hexapeptide antagonist PD 142893; it is essentially a truncated, single-residue variant used to probe what the receptor needs to see in order to bind.
History
The endothelin C-terminal hexapeptide, His-Leu-Asp-Ile-Ile-Trp (ET 16–21), was identified in the early 1990s as the minimum fragment of endothelin-1 that retains receptor binding, with the C-terminal tryptophan and the L-configuration of Trp-21 being essential for activity (Cody et al., J Med Chem 1995). The Parke-Davis group at Warner-Lambert built on that fragment by replacing the N-terminal histidine with bulky non-natural aromatic residues, producing the hexapeptide Ac-DDip-Leu-Asp-Ile-Ile-Trp — PD 142893 — a dual ETA/ETB receptor antagonist with low-nanomolar affinity at both subtypes (Cody et al., J Med Chem 1995). The SAR work in that paper systematically varied each residue of the hexapeptide to map the requirements for binding and for ETA-versus-ETB selectivity. The LDVIW pentapeptide on this card is one of the truncation/substitution analogs from that programme, indexed in ChEMBL as CHEMBL319660 with a reported IC50 of 17 nM.
What it does
In a radioligand binding assay against the endothelin A receptor, this peptide displaces labelled endothelin-1 with an IC50 of 17 nM (ChEMBL CHEMBL319660). That places it in the low-nanomolar potency range typical of the PD 142893 hexapeptide series. The natural ligand it competes with, endothelin-1, drives constriction of vascular smooth muscle and contributes to pathological remodelling of pulmonary vessels in disease; the broader rationale for studying ETA antagonists is that blocking endothelin signalling lowers pulmonary arterial pressure and improves haemodynamics in patients with pulmonary arterial hypertension, an effect now exploited clinically by the small-molecule antagonists bosentan (dual ETA/ETB) and ambrisentan (ETA-selective). LDVIW itself is a tool compound, not a therapeutic — its function in the literature is to define which side-chains of the endothelin C-terminus the receptor actually reads.
Mechanism
The C-terminal hexapeptide ET 16–21 is the pharmacophore the PD 142893 series is built on (Cody et al., J Med Chem 1995). Across that series, the key recognition elements are the C-terminal free carboxylate and L-Trp-21 (essential for ETB activity), the β-carboxylate of Asp-18, the Leu-17 side-chain, and a bulky residue at position 16. Replacing the N-terminal histidine with 3,3-diphenylalanine (DDip) — as in PD 142893 — converts the agonist hexapeptide fragment into a potent dual antagonist. LDVIW corresponds to the C-terminal five residues with isoleucine at position 19 replaced by valine; this is the kind of conservative isobutyl-to-isopropyl substitution used in SAR analysis to test how much steric bulk the receptor tolerates in that pocket. The 17 nM IC50 in ChEMBL is the readout of that probe at EDNRA.
Evidence
- Human: No clinical data on this peptide. It is a research ligand only.
- In vitro: Reported IC50 of 17 nM at the endothelin A receptor in the ChEMBL bioactivity record CHEMBL319660. The parent compound PD 142893 (Ac-DDip-Leu-Asp-Ile-Ile-Trp) was characterised as a dual ETA/ETB antagonist with low-nanomolar affinity in radioligand binding and functional assays (Cody et al., J Med Chem 1995).
- Animal: No animal data specific to LDVIW. The PD 142893 hexapeptide series was tested in vivo in vasoactive models in the original SAR programme but is metabolically unstable, with half-lives under 20 minutes in vitro before N-methylation strategies extended stability (Cody et al., J Med Chem 1995; subsequent hexapeptide stability work).
Regulatory status
- US: Not approved. Research chemical only; no human use.
- EU: Not approved.
- WADA: Not listed by name. The compound is a research peptide ligand and is not in clinical or athletic circulation.
This peptide is a ChEMBL-indexed research ligand, not a marketed drug. The therapeutic application of endothelin receptor antagonism is realised by the small-molecule drugs bosentan, ambrisentan, and macitentan, which are FDA- and EMA-approved for pulmonary arterial hypertension — none of those are peptides and none derive directly from this LDVIW series.
Related peptides
Other endothelin C-terminal pentapeptide and hexapeptide variants in the ChEMBL EDNRA SAR set are catalogued separately on the platform. The parent hexapeptide series (PD 142893, PD 145065) is the canonical reference point for understanding what this card is.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| IC50 | 17 nM | GPCRDB/ChEMBL |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.770 | global PDE — lower = better |
| disorder | 0.248 | fraction disordered |
| chain pair ipTM (A, B) | 0.852 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 313s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-23 |
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1 ▸citationbibtex
@peptide{pep10323,
sequence = {LDVIW},
target = {ednra},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}