Vasopressin-receptor research peptide (CHEMBL1817703)

What this is

This is a synthetic 8-residue peptide (sequence CFIQNCPG, ChEMBL identifier CHEMBL1817703) built on the vasopressin/oxytocin scaffold — two cysteines flanking a small ring, designed as a research-grade ligand of the vasopressin receptor family. It is a laboratory compound, not a drug: it has been characterized in a single medicinal-chemistry study (Wiśniewski et al., J. Med. Chem. 2011) as part of a series of "new, potent, selective, and short-acting peptidic V1a receptor agonists," and it sits in ChEMBL as a bioassay reference point rather than a clinical candidate. Compared with native arginine vasopressin (CYFQNCPRG), the cysteines at positions 1 and 6 are preserved — consistent with a vasopressin-family disulfide bridge that is not visible in the raw 8-letter sequence — while positions 2 and 3 are altered and the C-terminal arginine of vasopressin is absent. Its recorded potency at the V2 receptor is EC50 = 720 nM (CHEMBL1817703).

History

The compound was reported by Kazimierz Wiśniewski and colleagues at Ferring Research Institute in 2011 as part of a designed series of short-acting V1a-selective vasopressin analogs (Wiśniewski 2011). The series was published in the Journal of Medicinal Chemistry and was driven by structure-activity exploration around the cyclic nonapeptide vasopressin scaffold — the same scaffold that du Vigneaud's group at Cornell first synthesized and characterized in the early 1950s, work that won the 1955 Nobel Prize in Chemistry and established peptide-hormone chemistry as a tractable discipline. The compound has not been progressed to animal pharmacology or clinical development in the published record available here.

What it does

In assay systems it engages the vasopressin receptor family. Cards on this platform list its primary target as the V1a receptor (avpr1a) with secondary activity at V1b (avpr1b) and V2 (avpr2). V1a is the receptor that drives vasoconstriction on vascular smooth muscle; V1b sits on anterior pituitary corticotrophs and contributes to ACTH release; V2 is the renal receptor that controls water reabsorption. The Wiśniewski 2011 paper frames the series as agonists at V1a with a deliberately short duration of action — a design choice that distinguishes them from native vasopressin (plasma half-life ~10–20 minutes but with prolonged receptor effects) and from the long-acting analog desmopressin.

Evidence

• Human: No human trials published for this compound.
• Animal: No animal data in the references attached to this card.
• In vitro: Reported EC50 of 720 nM at V2 in the ChEMBL bioactivity record (CHEMBL1817703), characterized in the broader V1a-focused medicinal-chemistry series of Wiśniewski (2011).

Mechanism

Vasopressin-family receptors are G-protein-coupled receptors with distinct signaling outputs. V1a couples to Gq and triggers the phospholipase C / IP3 / DAG cascade, producing vascular smooth muscle contraction. V1b also couples to Gq and, on anterior pituitary corticotrophs, drives ACTH release as part of the stress axis. V2 couples to Gs and the cAMP/PKA pathway, driving trafficking of aquaporin-2 water channels to the apical membrane of renal collecting-duct principal cells and increasing water reabsorption. Because this compound is a designed analog of the cyclic vasopressin scaffold, it engages these same receptors but with substantially lower potency than the native hormone — the 720 nM V2 EC50 places it well below clinical-strength affinity, in line with its intended role as a structure-activity probe rather than a therapeutic.

Regulatory status

• US / EU: None. This is a research compound and is not an approved drug in any jurisdiction.
• WADA: Not specifically listed. The native hormone class falls under WADA's S5 (Diuretics and Masking Agents); this analog has no documented use in or out of competition.

Related peptides

• Vasopressin — the endogenous nine-amino-acid hormone (CYFQNCPRG) that this compound is built from.
• Desmopressin — the FDA-approved V2-selective vasopressin analog used clinically for central diabetes insipidus and bedwetting.
• Oxytocin — the sister cyclic nonapeptide hormone (CYIQNCPLG) that shares the disulfide-bridged scaffold and differs from vasopressin at only two positions.