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Twenty-one residues, two disulfide bridges, and the most potent vasoconstrictor the body makes — a peptide that is drugged by blocking it, never by giving it.
Also known as: ET-1 · Endothelin 1 · Big endothelin-1 (precursor)
Part of the Foundational & therapeutic peptides cluster
Overview
Endothelin-1 (ET-1) is a 21-amino-acid peptide with two disulfide bonds (Cys1–Cys15, Cys3–Cys11), produced by endothelial and vascular smooth-muscle cells, neurons and other tissues, and one of the most potent vasoconstrictors known. It is not a drug: it is the target of endothelin receptor antagonists, and its overactive signalling is implicated in cardiovascular disease and cancer.
Source & context
Biological / chemical source: Endothelial and vascular smooth-muscle cells, neurons, astrocytes and endometrial cells (human)
Primary research or clinical context: Endogenous peptide; not a medicine — it is the target of the endothelin receptor antagonists used in pulmonary arterial hypertension and kidney disease
What endothelin-1 is
Endothelin-1 “is a 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production,” as the IUPHAR Guide to Pharmacology summarises it. It was characterised in the late 1980s as “a potent vasoactive peptide” (Schini and Vanhoutte, Pharmacology and Toxicology 1991) and remains the reference vasoconstrictor against which others are measured. PubChem lists the human peptide at about 2,492 Da; IUPHAR notes that because it is defined by structure strings, several alternative database entries exist for the same molecule.
Sequence and the two disulfide bridges
The one-letter sequence is CSCSSLMDKECVYFCHLDIIW. Four cysteines form two disulfide bonds — “between cysteine residues at positions 1 and 15 and cysteine residues at positions 3 and 11” (IUPHAR post-translational modification note) — which fold the N-terminal two-thirds into a compact bicyclic core, leaving a hydrophobic C-terminal tail that ends in tryptophan and is essential for receptor binding. The peptide is cut from a longer precursor, big endothelin-1, by endothelin-converting enzyme, which is one of several points at which its signalling can be intercepted. The structure card above shows the residue classes; the two loops are what distinguish it from the linear vasoactive peptides elsewhere in the directory.
Receptors and why it is drugged by blocking
Endothelin-1 acts on two G-protein-coupled receptors, ETA and ETB. Its vasoconstrictor potency is such that there is no therapeutic use for giving it; instead, medicine targets it by antagonising the receptors, and the endothelin receptor antagonists are established treatments in pulmonary arterial hypertension and, more recently, kidney disease — the ClinicalTrials.gov snapshot for September 2026 includes a phase 1 trial of the antagonist sparsentan. A 2019 commentary asked whether “trapping endothelin-1” with a binding agent could extend the strategy to cardiovascular disease (Wernly and Jung, Drug Discovery Today 2019). The 58 registered studies naming endothelin-1 mostly measure it as a biomarker.
Endothelin-1 in disease
Beyond blood-vessel tone, ET-1 “is implicated in an array of diseases, and its signalling is often found to be overactivated within cancers,” where it “has been found to potentiate hallmarks of cancer progression such as cell proliferation, invasion and metastasis, as well as angiogenesis,” and to promote epithelial-mesenchymal transition and drug resistance (Harrison et al., Biomedicines 2024). The endothelin axis has been proposed as a therapeutic target in oral squamous cell carcinoma (Pazhani et al., Journal of Stomatology, Oral and Maxillofacial Surgery 2024). In cardiology it has been discussed as a biomarker in atrial cardiomyopathy (Matsubara and Fujiu, International Heart Journal 2019) and in cardio-oncology (Valero-Muñoz and Sam, JACC: CardioOncology 2023). IUPHAR also notes that plasma ET-1 correlated with clinical severity in COVID-19, prompting interest in receptor antagonists for some patients.
| Property | Value |
|---|---|
| Length | 21 residues |
| Disulfide bonds | Cys1–Cys15 and Cys3–Cys11 |
| Receptors | ETA and ETB |
| Precursor | Big endothelin-1, cleaved by endothelin-converting enzyme |
| Therapeutic role | Drug target (receptor antagonists), not a drug |
Relation to other peptides on this site
Endothelin-1 is the vasoconstrictor counterpart to vasopressin and angiotensin II, both of which are also endogenous pressor peptides, but it differs in that it has never been developed as a medicine. Its nearest structural relatives on the site are the other small disulfide-constrained peptides — the natriuretic peptides ANP and BNP, which are vasodilators with a single disulfide ring and are, in contrast, given therapeutically. The pairing of a bicyclic constrictor with monocyclic dilators makes endothelin-1 a good example of how disulfide topology and biological role are independent design variables.
Regulatory status
Endothelin-1 is an endogenous peptide and a laboratory reagent for receptor pharmacology; it has no marketing authorisation as a medicine anywhere, and none is sought. The drugs built around it are receptor antagonists, which are small molecules, not peptides, and are outside this directory's scope except as context. This profile is educational and is not guidance on obtaining or using any product.
Sequence
One-letter sequence commonly cited for Endothelin-1 (educational; isoforms and modifications may differ):
CSCSSLMDKECVYFCHLDIIW
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- 21-residue peptide with two disulfide bonds — Cys1–Cys15 and Cys3–Cys11 — forming a bicyclic core with a hydrophobic C-terminal tail ending in tryptophan
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Free acid (Trp21)
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C109H159N25O32S5
- Average reference mass
- ≈ 2,491.9
- Receptors
- Endothelin ETA and ETB receptors (class A G-protein-coupled receptors)
- Backbone
- 21-residue peptide with two disulfide bonds — Cys1–Cys15 and Cys3–Cys11 — forming a bicyclic core with a hydrophobic C-terminal tail ending in tryptophan
- C-terminus
- Free acid (Trp21)
- Status
- Endogenous peptide; not a medicine — the target of approved endothelin receptor antagonists as of September 2026
- PubChem CID: 16212950
- IUPHAR ligand: 989
- ChEMBL: CHEMBL3775234
- CAS RN: 123626-67-5
- UNII: 2K62B8Z6XF
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 58 registered studies with “Endothelin-1” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT02966665 | : Vascular Function in Health and Disease | Phase 1 | recruiting | 2026-09-25 |
| NCT07794475 | Effect of Trimetazidine on Endothelin-1 and Clinical Outcomes of Patients With Diabetic Peripheral Neuropathy | Phase 2 | recruiting | 2026-08-31 |
| NCT07224776 | Sparsentan for the Treatment of VEGF Signaling Pathway Inhibitor-Associated Proteinuria | Phase 1 | recruiting | 2026-07-30 |
| NCT07585006 | Comparative Evaluation of Nicotine Analogs | Phase 1 | recruiting | 2026-06-26 |
| NCT02086253 | Role of Endothelin-1 in Flow-mediated Dilatation | Not applicable | completed | 2026-06-12 |
| NCT07422974 | Perioperative Outcomes After Neoadjuvant Therapy in Colorectal Cancer | — | recruiting | 2026-02-20 |
Endothelin-1 — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: 21-residue peptide with two disulfide bonds — Cys1–Cys15 and Cys3–Cys11 — forming a bicyclic core with a hydrophobic C-terminal tail ending in tryptophanAverage reference mass: 2,491.9 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Endothelin-1
What is Endothelin-1?+
Endothelin-1 (ET-1) is a 21-amino-acid peptide with two disulfide bonds (Cys1–Cys15, Cys3–Cys11), produced by endothelial and vascular smooth-muscle cells, neurons and other tissues, and one of the most potent vasoconstrictors known. It is not a drug: it is the target of endothelin receptor antagonists, and its overactive signalling is implicated in cardiovascular disease and cancer.
What Canadian product status is recorded for Endothelin-1?+
Canadian product status for Endothelin-1 has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Endothelin-1?+
Endothelin-1 is commonly described as approximately 21 amino acids (Vasoconstrictor peptide).
What is endothelin-1?+
A 21-amino-acid peptide produced by endothelial cells, vascular smooth muscle, neurons and other tissues. It is one of the most potent vasoconstrictors in the body and also influences cell proliferation and hormone production.
What is the sequence of endothelin-1?+
CSCSSLMDKECVYFCHLDIIW, with disulfide bonds between Cys1–Cys15 and Cys3–Cys11.
Is endothelin-1 a drug?+
No. It is a drug target: endothelin receptor antagonists block its ETA and ETB receptors in pulmonary arterial hypertension and kidney disease.
What does endothelin-1 do in cancer?+
Its signalling is often overactivated in tumours, where it promotes proliferation, invasion, metastasis, angiogenesis and drug resistance, according to a 2024 review.
How is endothelin-1 made in the body?+
It is cleaved from a longer precursor, big endothelin-1, by endothelin-converting enzyme.
Related peptides
References & further reading
- 1.Rayner et al. (2020). In reply, endothelin-1 and the Anrep effect. J Heart Lung Transplant
- 2.Bouchama et al. (1995). Endothelin-1 in heatstroke. J Appl Physiol (1985)
- 3.Matsubara et al. (2019). Endothelin-1 and Atrial Cardiomyopathy. Int Heart J
- 4.Valero-Muñoz et al. (2023). Endothelin-1: Is it Time to "Biomark" the Cardiac-Tumor-Treatment Nexus in Breast Cancer?. JACC CardioOncol
- 5.Harrison et al. (2024). Endothelin-1 and Its Role in Cancer and Potential Therapeutic Opportunities. Biomedicines
- 6.Rozen et al. (1996). [Endothelin-1]. Harefuah
- 7.Pazhani et al. (2024). Endothelin-1 axis as a therapeutic target in oral squamous cell carcinoma: Molecular insights. J Stomatol Oral Maxillofac Surg
- 8.Wernly et al. (2019). Trapping endothelin-1 to hunt down cardiovascular disease?. Drug Discov Today
- 9.Schini & Vanhoutte (1991). Endothelin-1: a potent vasoactive peptide. Pharmacology & Toxicology
- 10.IUPHAR/BPS Guide to Pharmacology — endothelin-1, ligand 989
- 11.PubChem — Endothelin-1 (CID 16212950)