Endothelin-1 (11-21), also known as IRL 1038, is an 11-residue cyclic fragment derived from the C-terminal region of human Endothelin-1. The peptide contains the sequence Cys-Val-Tyr-Phe-Cys-His-Leu-Asp-Ile-Ile-Trp and forms an intramolecular disulfide bond between Cys1 and Cys5.

Unlike full-length Endothelin-1, which activates both ETA and ETB receptors, this defined fragment has been characterized as an ETB receptor-selective peptide antagonist. It is therefore useful for separating ETB-mediated responses from ETA-dependent signaling in vascular and receptor pharmacology experiments.

Product Information

A Cyclic C-Terminal Fragment of Endothelin-1

Full-length human Endothelin-1 contains 21 residues and two disulfide bridges. Endothelin-1 (11-21) isolates the C-terminal half of the native molecule while retaining Cys11 and Cys15, which form a new intramolecular disulfide linkage in the truncated peptide.

When the fragment is renumbered from its own N-terminus, this bond is described as Cys1-Cys5. In full-length ET-1 numbering, the same linkage is represented as Cys11-Cys15.

This cyclic structure distinguishes IRL 1038 from linear ET-1 fragments and contributes to its characteristic receptor-binding profile.

Selective Antagonism at the ETB Receptor

Classical receptor-binding experiments showed that IRL 1038 has substantially higher affinity for ETB receptors than for ETA receptors. Reported inhibition constants were approximately 6-11 nM at ETB compared with approximately 0.4-0.7 µM at ETA under the study conditions.

Functional experiments also showed that the peptide inhibited ETB-mediated smooth-muscle contraction without significant agonist activity in the tested systems.

We recommend treating these affinity values as assay-specific reference data rather than fixed product specifications, because apparent potency can vary with receptor species, tissue preparation and experimental format.

ETB Blockade Can Reveal Opposing Vascular Pathways

ETB receptors can contribute to vascular biology in ways that differ from ETA receptors. In endothelial systems, ETB activation can support nitric oxide-dependent vasodilatory responses, while ETA signaling is strongly associated with vascular smooth-muscle contraction.

IRL 1038 has been used experimentally to isolate this ETB component. In isolated rat heart studies, ETB blockade with IRL 1038 enhanced ET-1-induced coronary vasoconstriction, consistent with removal of an opposing ETB-dependent vasodilatory contribution.

This makes the peptide useful for experiments in which total ET-1 activity needs to be separated into receptor-subtype-specific components.

Full-Length Endothelin-1 and IRL 1038 Serve Different Roles

The two peptides should therefore not be described as functionally interchangeable fragments of the same ligand.

Researchers studying the native agonist can also review Human Endothelin-1.

Structure–Activity Considerations

The C-terminal region of ET-1 contributes strongly to endothelin receptor recognition, particularly the hydrophobic residues approaching Trp21. IRL 1038 preserves this receptor-facing C-terminal sequence while substantially changing the overall disulfide architecture of the parent hormone.

Its pharmacology therefore illustrates how truncation and controlled cyclization can convert a dual-receptor agonist scaffold into a receptor-subtype-selective antagonist.

Analytical and Handling Considerations

Correct disulfide formation is part of the intended molecular identity. A reduced form with two free cysteine residues is not structurally equivalent to IRL 1038.

The peptide also contains multiple hydrophobic aromatic residues, including Tyr, Phe and Trp, which can influence chromatographic retention and solution behavior.

For quantitative receptor studies, we recommend confirming molecular mass together with chromatographic purity. Our Peptide Quality Control capabilities support analytical HPLC and mass spectrometry according to the selected specification.

Research Applications

Endothelin-1 (11-21) can support ETB receptor pharmacology, antagonist competition studies, vascular smooth-muscle experiments, endothelial signaling research, receptor-subtype discrimination and endothelin peptide structure–activity studies.

Related vasoactive and inflammatory mediators are available in our Pain and Inflammation Modulation Peptides collection.

Endothelin fragments, cyclized analogs and receptor-directed sequence variants can also be evaluated through Chemical Peptide Synthesis.

Frequently Asked Questions

Is Endothelin-1 (11-21) the same as IRL 1038?

Yes. The cyclic peptide CVYFCHLDIIW with a Cys1-Cys5 disulfide bridge is commonly known as IRL 1038 or [Cys11-Cys15]-Endothelin-1 (11-21).

Is IRL 1038 an endothelin receptor agonist?

It is primarily characterized as an ETB-selective antagonist. Classical functional studies reported inhibition of ETB-mediated responses without significant agonist activity under the tested conditions.

Why is the disulfide sometimes written Cys11-Cys15 and sometimes Cys1-Cys5?

Cys11 and Cys15 refer to positions in full-length Endothelin-1. After residues 11-21 are isolated as an 11-residue fragment, those same cysteines become positions 1 and 5.

Can linear or modified IRL 1038 analogs be synthesized?

Linearized variants, alternative cyclization patterns and residue-substituted endothelin fragments can be evaluated through Chemical Peptide Synthesis.

Research Use Only.