Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.
Twenty-eight residues, two receptors shared with PACAP, and a half-life too short to be a drug without re-engineering.
Also known as: vasoactive intestinal peptide · vasoactive intestinal polypeptide
Part of the Foundational & therapeutic peptides cluster
Overview
Vasoactive intestinal peptide (VIP) is a 28-residue neuropeptide (HSDAVFTDNYTRLRKQMAVKKYLNSILN) first isolated from pig small intestine and identical in humans, mice and rats. It acts through the VPAC1 and VPAC2 receptors it shares with PACAP, relaxes smooth muscle, dilates vessels, modulates immunity and helps set the circadian clock. Native VIP is degraded within minutes; an inhaled formulation was evaluated for pulmonary hypertension in COPD without further development.
Source & context
Biological / chemical source: Endogenous neuropeptide
Primary research or clinical context: Endogenous neuropeptide; native VIP was evaluated as an inhaled therapy for pulmonary hypertension in COPD without further development; no VIP product is approved in North America or the EU
What VIP is
Vasoactive intestinal peptide is a 28-amino-acid neuropeptide first isolated and sequenced from pig small intestine; the human, mouse and rat sequences are identical (IUPHAR ligand 1152). It belongs to the secretin–glucagon superfamily alongside PACAP, secretin, glucagon and GLP-1, and its name records its first-observed action — dilating blood vessels — and its site of discovery. It is a widespread neurotransmitter with roles ranging from growth regulation, sexual function, bronchodilation and vasodilation to immune interactions and neurotrophism (Gozes and Furman, Current Pharmaceutical Design 2003). VIP-immunoreactive nerve fibres were mapped in the gallbladder of several mammals including humans as early as 1977 (Sundler et al., Gastroenterology).
Receptors: VPAC1 and VPAC2
VIP's physiological and pathophysiological actions are mediated by two class B G-protein-coupled receptors, VPAC1 and VPAC2, which also bind PACAP (Igarashi et al., Journal of Pharmacology and Experimental Therapeutics 2005). VPAC1 predominates in the gastrointestinal tract, which is why native VIP causes GI side effects; VPAC2 is prominent in the heart, smooth muscle and the suprachiasmatic nucleus. Structure–activity work has produced simplified analogues with more than 2,000-fold selectivity for one receptor over the other, by alanine-scanning the native sequence (Igarashi et al., 2005) — the toolkit that any VIP-based drug would need.
Physiology beyond the gut
In the intestinal epithelium VIP promotes secretory differentiation via the p38 MAPK pathway and modulates proliferation of Lgr5+ progenitor cells, with effects on radiation injury in vitro (Agibalova et al., Stem Cell Research and Therapy 2024). In the brain's master clock, reduced VIP expression in a common VIP-Cre mouse line altered circadian function (Joye et al., Journal of Biological Rhythms 2020), and VIP-expressing interneurons in motor cortex show distinctive short-term plasticity (McFarlan et al., Frontiers in Synaptic Neuroscience 2024). Neuroendocrine-cell-derived VIP is implicated in allergic disease (Verma et al., Cytokine and Growth Factor Reviews 2017), and ovarian VIP regulates fibro-inflammation and foamy macrophage generation in premature ovarian ageing (Castagnola et al., Molecular and Cellular Endocrinology 2025).
Clinical evaluation and why it stalled
Native VIP was evaluated by inhalation for pulmonary hypertension in COPD patients (NCT00464932); the study completed with no indication of further development. The IUPHAR record gives the reasons: a short circulating half-life and gastrointestinal side effects driven by VPAC1 receptors. To overcome both, PhaseBio developed a conjugated VIP analogue with an extended half-life of about 60 hours and selectivity for myocardial VPAC2 receptors, coded PB1046 (IUPHAR record). The pattern — potent hormone, minutes of half-life, a re-engineered analogue to make a drug of it — is the same one that produced the GLP-1 medicines.
| Molecule | Feature | Status per sources |
|---|---|---|
| Native VIP (inhaled) | Evaluated for pulmonary hypertension in COPD (NCT00464932) | Completed; no further development |
| Alanine-scanned analogues | >2,000-fold VPAC1 or VPAC2 selectivity | Research tools (Igarashi et al., 2005) |
| PB1046 (conjugate) | ≈ 60-hour half-life; myocardial VPAC2 selectivity | Development-stage (IUPHAR record) |
Pharmacokinetics
Native VIP is rapidly degraded in the circulation, a limitation the IUPHAR record cites as the barrier to clinical use, and metabolically stable simplified analogues had to be designed to study the receptors properly (Igarashi et al., 2005). The PB1046 conjugate's roughly 60-hour half-life shows the scale of extension that protein fusion or conjugation can achieve. Precise human half-life values for native VIP are not stated in the abstracts reviewed beyond “short.”
Regulatory status as of September 2026
No VIP product is an approved medicine in the United States, Canada or the European Union. VIP is sold in the grey market as a “research peptide” — often with claims about inflammation or chronic infections that have no clinical trial behind them; such vials are unlicensed and of unverified content. Registry searches for “VIP” return more than a hundred studies, nearly all unrelated uses of the acronym.
VIP vs PACAP and the secretin family
PACAP is VIP's closest relative, shares both VPAC receptors and adds its own PAC1 receptor; the two are the reason receptor-selective analogues are hard to make. Secretin, glucagon, GLP-1 and GIP are the same superfamily's better-known members, and the GLP-1 story shows what happens when a minutes-long hormone is re-engineered for stability. The receptor-classes guide sets the family out.
Sequence
One-letter sequence commonly cited for VIP (educational; isoforms and modifications may differ):
HSDAVFTDNYTRLRKQMAVKKYLNSILN
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
- 28 residues, C-terminally amidated; sequence identical in human, mouse and rat; first isolated and sequenced from porcine small intestine
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Amide
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-09-06
- PubChem molecular record · 2026-09-06
- Molecular formula
- C147H237N43O43S
- Average reference mass
- ≈ 3,326.8
- Plasma half-life
- Minutes: native VIP is rapidly degraded, which limits clinical use (IUPHAR record); an engineered conjugate, PB1046, extended the half-life to roughly 60 hours
- Receptors
- VPAC1 and VPAC2 (class B GPCRs, shared with PACAP); VPAC1 predominates in the gastrointestinal tract and drives the GI side effects of native VIP
- Backbone
- 28 residues, C-terminally amidated; sequence identical in human, mouse and rat; first isolated and sequenced from porcine small intestine
- C-terminus
- Amide
- Status
- Endogenous hormone; not an approved drug. Registry hits for 'VIP' are mostly unrelated acronyms (snapshot September 2026)
- PubChem CID: 16129679
- IUPHAR ligand: 1152
- UNII: NS00125911
Chemistry values: curated profile, IUPHAR/BPS Guide to Pharmacology, PubChem · fetched 2026-09-06.
Clinical development snapshot
ClinicalTrials.gov lists 127 registered studies with “VIP” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT06835556 | Volatility in Paranoia (VIP) Trial: An RCT of Changes in Volatility With Psychotherapy | Not applicable | recruiting | 2026-09-30 |
| NCT07832032 | Biological Profiles of Neuropeptides, Neurotrophins and miRNA in Migraine | — | not yet recruiting | 2026-09-21 |
| NCT06735950 | The Volunteering-in-Place Program for Apathetic Assisted Living Residents With ADRD | Not applicable | not yet recruiting | 2026-09-17 |
| NCT07819110 | Radicle HealthTM VIP: A Study Assessing the Impact of Health and Wellness Products on Metabolic Health and Rel | Not applicable | not yet recruiting | 2026-09-14 |
| NCT05547698 | A Study of Venoarterial ECMO vs Off-Pump Bilateral Orthotopic Lung Transplantation | Not applicable | recruiting | 2026-09-10 |
| NCT06797336 | A Study of PT0253 in Participants With KRAS G12D Mutated Advanced Solid Tumors | Phase 1 | recruiting | 2026-08-12 |
VIP — 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: 28 residues, C-terminally amidated; sequence identical in human, mouse and rat; first isolated and sequenced from porcine small intestineAverage reference mass: 3,326.8 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.
- Trials2 registered studies added on ClinicalTrials.gov (now 127).
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about VIP
What is VIP?+
Vasoactive intestinal peptide (VIP) is a 28-residue neuropeptide (HSDAVFTDNYTRLRKQMAVKKYLNSILN) first isolated from pig small intestine and identical in humans, mice and rats. It acts through the VPAC1 and VPAC2 receptors it shares with PACAP, relaxes smooth muscle, dilates vessels, modulates immunity and helps set the circadian clock. Native VIP is degraded within minutes; an inhaled formulation was evaluated for pulmonary hypertension in COPD without further development.
What Canadian product status is recorded for VIP?+
Canadian product status for VIP 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 VIP?+
VIP is commonly described as approximately 28 amino acids (Neuropeptide).
What is VIP?+
Vasoactive intestinal peptide, a 28-residue neuropeptide that relaxes smooth muscle, dilates vessels, modulates immunity and helps regulate the circadian clock, acting through VPAC1 and VPAC2 receptors.
What is the sequence of VIP?+
HSDAVFTDNYTRLRKQMAVKKYLNSILN, C-terminally amidated; identical in humans, mice and rats.
Is VIP an approved drug?+
No. Inhaled native VIP was evaluated for pulmonary hypertension in COPD without further development; an engineered long-acting analogue, PB1046, was developed to overcome its short half-life.
What is VIP's half-life?+
Minutes — native VIP is rapidly degraded, which is why analogues with extended half-lives (about 60 hours for PB1046) were designed.
VIP vs PACAP?+
Both bind VPAC1 and VPAC2; PACAP also activates its own PAC1 receptor. They are close relatives in the secretin–glucagon superfamily.
Why does VIP cause GI side effects?+
VPAC1 receptors are concentrated in the gastrointestinal tract, so systemic VIP acts there first (IUPHAR record).
Further reading
- PK conceptsWhy Peptides Have Short Half-Lives (And How Engineers Fix It)Proteases, renal clearance, DPP-4, PEGylation, lipidation, cyclization—educational guide to peptide pharmacokinetics concepts.
- FoundationsGLP-1 vs GIP vs Glucagon: Incretin Receptor Classes ExplainedAn educational overview of the incretin and metabolic receptor classes—GLP-1, GIP, and glucagon—and how single, dual, and triple receptor agonism differ mechanistically.
- FoundationsWhat Are Research Peptides? A Clear Educational GuideLearn what “research peptides” means, how they differ from approved peptide drugs, quality markers (COA, purity), and how to study them responsibly.
Related peptides
References & further reading
- 1.Foster (2012). Editorial: vasoactive intestinal peptide (vip): historic perspective and future potential. Endocr Metab Immune Disord Drug Targets
- 2.Zhang et al. (2022). Vasoactive Intestinal Peptide (VIP) Protects Nile Tilapia (Oreochromis niloticus) against Streptococcus agalatiae Infection. Int J Mol Sci
- 3.Flood et al. (1990). Vasoactive intestinal peptide (VIP): an amnestic neuropeptide. Peptides
- 4.Klippstein et al. (2015). Vasoactive Intestinal Peptide (VIP) Nanoparticles for Diagnostics and for Controlled and Targeted Drug Delivery. Adv Protein Chem Struct Biol
- 5.Pandol et al. (1986). Vasoactive intestinal peptide receptor antagonist [4Cl-D-Phe6, Leu17] VIP. Am J Physiol
- 6.Bryant (1978). Vasoactive intestinal peptide (VIP). J Clin Pathol Suppl (Assoc Clin Pathol)
- 7.Korkmaz et al. (2025). Vasoactive Intestinal Peptide (VIP) and its Receptors in Adipose Tissue: Implications for Cold Stress Adaptation. Cell Biochem Biophys
- 8.Dufes et al. (2003). Brain delivery of vasoactive intestinal peptide (VIP) following nasal administration to rats. Int J Pharm
- 9.Igarashi et al. (2005). Development of simplified vasoactive intestinal peptide analogs with receptor selectivity and stability for human VIP/PACAP receptors. Journal of Pharmacology and Experimental Therapeutics
- 10.Gozes & Furman (2003). VIP and drug design. Current Pharmaceutical Design
- 11.Agibalova et al. (2024). Vasoactive intestinal peptide promotes secretory differentiation and mitigates radiation-induced intestinal injury. Stem Cell Research and Therapy
- 12.Joye et al. (2020). Reduced VIP expression affects circadian clock function in VIP-IRES-CRE mice. Journal of Biological Rhythms
- 13.Verma et al. (2017). Neuroendocrine cells derived chemokine vasoactive intestinal polypeptide (VIP) in allergic diseases. Cytokine and Growth Factor Reviews
- 14.Sundler et al. (1977). VIP innervation of the gallbladder. Gastroenterology
- 15.IUPHAR/BPS Guide to Pharmacology — VIP, ligand 1152