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Vasoactive intestinal peptide (VIP, aviptadil) / Studies
Natural peptide · 28 amino acids · 3,325.8 Da

Vasoactive intestinal peptide (VIP, aviptadil) studies and research data

PepBank has 420 VIP peptide studies with results. 218 of them gave VIP peptide, with 887 results, grouped by what the studies measured. In each group, results from studies in people come first. Data as of 2026-10-30.

Searches 887 results and 4,582 papers. Newer studies from Europe PMC

Results in people
212
24% of 887 results
Results in animals
267
30% of 887 results
Results in lab cells
408
46% of 887 results
From computer models
0
0% of 887 results
The molecule

VIP peptide identity

Identifiers, parent molecule, targets and development stage, from curated data.

Vasoactive intestinal peptide (VIP) is a linear peptide amide of 28 residues (HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2) with a free N-terminus and no disulfide bond. It is cut from the 170-residue human precursor (UniProt P01282, VIP_HUMAN) at positions 125-152, and Asn152 is amidated. The same 28 residues are in the UniProt entries for mouse, rat, cattle, pig and other mammals. Aviptadil is the INN of synthetic VIP with this sequence. VIP binds the class B receptors VPAC1 and VPAC2 with high affinity. PAC1 is selective for PACAP. Most of the literature is about the body's own VIP (gut, nerves, brain, immune cells). As a drug, aviptadil is authorised only inside Invicorp (aviptadil 25 micrograms with phentolamine 2 mg, injected into the penis) for erectile dysfunction, for example in Sweden since 2015-05-07. FDA has not approved it and EMA has not centrally authorised it. The largest trial of aviptadil alone, TESICO (phase 3, NIAID, COVID-19 respiratory failure, 471 people randomised), found no benefit at day 90 (odds ratio 1.11, 95% CI 0.80-1.55) and stopped for futility in 2022. FDA lists 'Vasoactive Intestinal Peptide' in 503A compounding category 1 (under evaluation).

Kind
Natural peptide · 28 residues
Identifiers
UniProtP01282 (opens in a new tab)PubChem CID66577104 (opens in a new tab)16140438 (opens in a new tab)UNIIA67JUW790C (opens in a new tab)DrugBankDB06260 (opens in a new tab)CAS40077-57-437221-79-7PDB8E3Z (opens in a new tab)9P92 (opens in a new tab)9P93 (opens in a new tab)KEGGD12127 (opens in a new tab)
Development
Approved only in a combination product (aviptadil with phentolamine) in some European countriesEvolan Pharma AB (marketing authorisation holder of Invicorp, aviptadil + phentolamine, for erectile dysfunction). Other sponsors of aviptadil work: APR Applied Pharma Research s.a. (lead sponsor of the Zyesami COVID-19 trials on ClinicalTrials.gov), Relief Therapeutics International SA (FDA orphan designation 2020, sarcoidosis), NIAID (ACTIV-3b/TESICO), Mondobiotech (orphan designations 2001-2007), Clinicuro ApS (EU orphan designation 2026, ARDS). No active developer was confirmed.'approved' here means authorised as one part of the combination Invicorp for erectile dysfunction (Sweden, UK, France). Aviptadil alone is not approved anywhere that was checked. Aviptadil alone: highest registered phase is phase 3. NCT04843761 and NCT06729606 (ACTIV-3b/TESICO, NIAID, phase 3, completed, start 2021-04-20; 473 and 471 people) were published in Lancet Respir Med 2023 (PMID 37348524): aviptadil versus placebo at day 90, odds ratio 1.11 (95% CI 0.80-1.55), stopped for futility on 2022-05-25. NCT04311697 (phase 2/3, intravenous aviptadil, critical COVID-19, APR Applied Pharma Research, 203 people, completed 2021-02-22; Crit Care Med 2022, PMID 36044317): primary endpoint not significant (odds ratio 1.6, 95% CI 0.86-3.11). NCT04360096 (phase 2/3, inhaled, terminated, sponsor decision), NCT05137795 (phase 3, withdrawn, 0 people), NCT04844580 (phase 2, completed, 80 people) and NCT04536350 (phase 2, inhaled, Basel, terminated for slow recruitment). NCT00004494 (phase 1, ARDS, Stony Brook, 18 people, start 1998-09). Experimental VIP infusions in healthy people and migraine patients (Danish Headache Center, phase NA). ChEMBL records max phase 3 (CHEMBL1981592). The 'PHASE4' value in the r18i research file comes from NCT03898856, a crofelemer trial in which a VIP blood level is one diagnostic test; it is not a VIP or aviptadil trial. PB1046 (pemziviptadil), a long-acting VIP analogue (PhaseBio, NCT03315507, NCT03556020, NCT04433546), is a different substance. No ClinicalTrials.gov record that gives aviptadil and starts after 2022 was found. ISRCTN and EU CTIS were not searchable. Source (opens in a new tab)

Targets

Molecular targets with action and evidence source
TargetActionEvidence
Vasoactive intestinal polypeptide receptor 1 (VPAC1)VIPR1P32241 (opens in a new tab)Agonist (high affinity; vip and pacap both activate it)IUPHAR review (2012) and cryo-EM structure of the VIP-VPAC1-Gs complex (PDB 8E3Z, 2022)Source (opens in a new tab)
Vasoactive intestinal polypeptide receptor 2 (VPAC2)VIPR2P41587 (opens in a new tab)Agonist (high affinity)primary literature: human VPAC2 binding IC50 for VIP 9.4 nM; cAMP ED50 2.2 nM (PMID 8933357); IUPHAR reviewSource (opens in a new tab)
Pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1)ADCYAP1R1P41586 (opens in a new tab)Weak agonist (pac1 is selective for pacap; vip complexes with pac1 splice variants have been solved, pdb 9p92 and 9p93)IUPHAR review (PAC1 selective for PACAP) and cryo-EM / molecular dynamics study (VIP selective for VPAC1 over PAC1)Source (opens in a new tab)

Sequence and structure

Residues, differences from the parent, calculated properties and 3D structure. Source values and calculated values are shown separately.

Sequence

28 amino acids · 1 modification

H-
Residues 1 to 10:
HSDAVFTDNY
Residues 11 to 20:
TRLRKQMAVK
Residues 21 to 28:
KYLNSILN
  • HydrophobicA V I L M
  • AromaticF W Y
  • PositiveK R H
  • NegativeD E
  • PolarS T N Q
  • Modified residue

Modifications

Asn28-NH2
C-terminal amide
C-terminal asparagine amide. UniProt P01282 lists 'Asparagine amide' at 152 (mature position 28). GSRS aviptadil A67JUW790C names it '...-Asn-NH2' ('L-aspartamide') and gives formula C147H238O42N44S.

Properties

From identity sources

Formula
C147H238N44O42S
Molecular weight
3,325.8 g/mol
Monoisotopic mass
3,323.7561 Da

Calculated from the sequence

Average mass
3,325.84 Da
Sum of ExPASy residue masses + water + C-amide · ExPASy Compute pI/Mw; FindMod
Monoisotopic mass
3,323.7561 Da
Sum of ExPASy residue masses + water + C-amide · ExPASy FindMod
Isoelectric point (pI)
10.72
pH of zero net charge, EMBOSS pKa set · EMBOSS iep, Epk.dat
Net charge at pH 7.4
4.05
Henderson-Hasselbalch, EMBOSS pKa set · EMBOSS iep, Epk.dat
GRAVY (hydropathy)
−0.639
Mean Kyte-Doolittle hydropathy · Kyte and Doolittle 1982
Negative: hydrophilic on average.
Extinction coefficient, 280 nm (Cys reduced)
2,980 M⁻¹ cm⁻¹
5500 x Trp + 1490 x Tyr · Pace et al. 1995 (ExPASy ProtParam)
No Trp: ExPASy reports more than 10 % error without Trp.
Instability index
32.19
Dipeptide instability weights (DIWV) · Guruprasad et al. 1990
40 or below: classed as stable (ExPASy).
Aliphatic index
83.6
Mole % A + 2.9 V + 3.9 (I + L) · Ikai 1980
Boman index
2.48 kcal/mol
Mean solubility value (negated) · Boman 2003
Above 2.48: high protein-binding potential (Boman).
Hydrophobic moment (μH)
0.599
Eisenberg scale, 100° per residue, best 11-residue window · Eisenberg et al. 1982, 1984
pI with each pKa set
EMBOSS 10.72Bjellqvist (ExPASy) 10.17IPC peptide 10.55IPC protein 10.10
  • Defined and validated for proteins; use with care for short peptides.
  • Assumes an ideal alpha helix. Many short peptides are not helical.

@pepdb/chem 0.2.0 · EMBOSS pKa set · ExPASy residue masses

Net charge by pH

pI 10.72 · Net charge at pH 7.4: 4.05

Point or use arrow keys

Net charge of Vasoactive intestinal peptide (VIP, aviptadil) from pH 0 to 14 (EMBOSS pKa set). Isoelectric point 10.72. Net charge at pH 7.4: 4.05.−50+5+1002468101214pHNet chargepH 7.4pI 10.72

Henderson-Hasselbalch, EMBOSS pKa set, C-amide. Calculated, not measured.

Show as table
pHNet charge
07.00
17.00
26.98
36.78
45.88
55.12
64.77
74.22
83.81
93.09
101.74
11−0.67
12−2.28
13−3.50
14−3.94

Composition

  • Hydrophobic32% (9)
  • Aromatic11% (3)
  • Positive21% (6)
  • Negative7% (2)
  • Polar29% (8)

28 residues. Each residue counts in one class; F and W count as aromatic.

A Ala2 · 7%
I Ile1 · 4%
L Leu3 · 11%
M Met1 · 4%
V Val2 · 7%
F Phe1 · 4%
W Trp0 · 0%
Y Tyr2 · 7%
H His1 · 4%
K Lys3 · 11%
R Arg2 · 7%
D Asp2 · 7%
E Glu0 · 0%
N Asn3 · 11%
Q Gln1 · 4%
S Ser2 · 7%
T Thr2 · 7%
C Cys0 · 0%
G Gly0 · 0%
P Pro0 · 0%

3D structure

ExperimentalPDB 8E3Z

Loads the 3D viewer (3Dmol.js, about 150 KB) and the model file from RCSB PDB.

RCSB Protein Data Bank · CC0 1.0

2D structure

Vasoactive intestinal peptide (VIP, aviptadil) has 28 residues. A full-atom drawing is hard to read at this size; the sequence view is the reference.

SMILES fromPubChem CID 66577104(opens in a new tab)

CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)N)C(=O)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC4=CNC=N4)N

Helical wheel

An ideal alpha-helix projection. It shows where the hydrophobic residues fall if the peptide folds as a helix. It does not show that it does.

Helical wheel of Vasoactive intestinal peptide (VIP, aviptadil), 28 residues at 100 degrees per residue. Hydrophobic moment 0.12 pointing at 34 degrees.His 1, Eisenberg consensus (normalized) -0.40H1Ser 2, Eisenberg consensus (normalized) -0.18S2Asp 3, Eisenberg consensus (normalized) -0.90D−3Ala 4, Eisenberg consensus (normalized) 0.62A4Val 5, Eisenberg consensus (normalized) 1.08V5Phe 6, Eisenberg consensus (normalized) 1.19F6Thr 7, Eisenberg consensus (normalized) -0.05T7Asp 8, Eisenberg consensus (normalized) -0.90D−8Asn 9, Eisenberg consensus (normalized) -0.78N9Tyr 10, Eisenberg consensus (normalized) 0.26Y10Thr 11, Eisenberg consensus (normalized) -0.05T11Arg 12, Eisenberg consensus (normalized) -2.53R+12Leu 13, Eisenberg consensus (normalized) 1.06L13Arg 14, Eisenberg consensus (normalized) -2.53R+14Lys 15, Eisenberg consensus (normalized) -1.50K+15Gln 16, Eisenberg consensus (normalized) -0.85Q16Met 17, Eisenberg consensus (normalized) 0.64M17Ala 18, Eisenberg consensus (normalized) 0.62A18Val 19, Eisenberg consensus (normalized) 1.08V19Lys 20, Eisenberg consensus (normalized) -1.50K+20Lys 21, Eisenberg consensus (normalized) -1.50K+21Tyr 22, Eisenberg consensus (normalized) 0.26Y22Leu 23, Eisenberg consensus (normalized) 1.06L23Asn 24, Eisenberg consensus (normalized) -0.78N24Ser 25, Eisenberg consensus (normalized) -0.18S25Ile 26, Eisenberg consensus (normalized) 1.38I26Leu 27, Eisenberg consensus (normalized) 1.06L27Asn 28, Eisenberg consensus (normalized) -0.78N28
μH, residues shown
0.123
μH, best 11-residue window
0.599
Arrow direction
34°
Residues
28 · 2 rings of 18
HydrophilicHydrophobic

Eisenberg consensus (normalized) scale · + K, R · − D, E

Assumes an ideal α-helix: 100° per residue, 3.6 residues per turn. The arrow is the mean hydrophobic moment (Eisenberg et al. 1984) and points at the hydrophobic face.

Show as table
PositionResidueAngleEisenberg consensus (normalized)
1H0°-0.40
2S100°-0.18
3D200°-0.90
4A300°0.62
5V40°1.08
6F140°1.19
7T240°-0.05
8D340°-0.90
9N80°-0.78
10Y180°0.26
11T280°-0.05
12R20°-2.53
13L120°1.06
14R220°-2.53
15K320°-1.50
16Q60°-0.85
17M160°0.64
18A260°0.62
19V0°1.08
20K100°-1.50
21K200°-1.50
22Y300°0.26
23L40°1.06
24N140°-0.78
25S240°-0.18
26I340°1.38
27L80°1.06
28N180°-0.78
Results by area

What the studies measured

People first in each area, then animals, then lab cells. Counts are exact and come from studies that gave the peptide.

Trials and papers
Status and safety
Data