VIP

Vasoactive Intestinal Peptide (VIP) is a naturally occurring 28-amino-acid neuropeptide produced throughout the human body, with especially high concentrations in the gastrointestinal tract, central and peripheral nervous systems, and lung tissue. Its molecular formula is C147H237N43O43S, with PubChem CID 53314964 and CAS number 40077-57-4. Despite its name, VIP's research applications extend well beyond intestinal or vascular physiology into pulmonary, immunological, and neurological contexts.

At Verified Peptides, we point researchers to VIP's synthetic pharmaceutical form, aviptadil (marketed under the development code RLF-100 by Relief Therapeutics and its partners), as the most clinically advanced version of this molecule. Aviptadil holds a genuinely distinctive regulatory position among the compounds in our catalog: it carries FDA and European Union Orphan Drug Designations for acute respiratory distress syndrome (ARDS), pulmonary arterial hypertension, and sarcoidosis, and a related VIP-based formulation (in combination with phentolamine) is already marketed in parts of Europe for erectile dysfunction. This makes VIP one of the few compounds in this catalog with an existing approved indication somewhere in the world, even though it remains unapproved for the orphan-designated respiratory and pulmonary indications that represent its primary current research focus.

VIP has more than a 20-year history of use in human clinical research across sarcoidosis, pulmonary fibrosis, and pulmonary hypertension studies, giving it an unusually long and varied published safety record compared with many newer investigational peptides. This extended human-use history is itself part of what made VIP an attractive rapid-repurposing candidate when the COVID-19 pandemic created urgent demand for compounds with pre-existing safety data, since starting clinical trials with an entirely novel molecule typically requires substantially more preliminary safety work before human dosing can even begin.

At Verified Peptides, we consider VIP/aviptadil's clinical evidence base one of the more genuinely mixed and evolving stories in our current catalog, spanning several distinct disease contexts with different outcomes in each. In primary pulmonary hypertension, an early study (Petkov V, et al., Journal of Clinical Investigation, 2003; PMID 12727925) found that intravenous VIP decreased mean pulmonary artery pressure and increased cardiac output and mixed venous oxygen saturation in a small cohort of 8 patients, establishing early proof-of-concept for VIP's pulmonary vasodilator activity in humans.

During the COVID-19 pandemic, aviptadil was rapidly studied as a candidate for critical respiratory failure. A randomized, placebo-controlled trial across ten U.S. hospitals (approximately 196 patients, 2:1 randomization to IV aviptadil or placebo; Critical Care Medicine, 2022; PMID 36044317) did not meet its primary endpoint (alive and free of respiratory failure at day 60), but found a statistically significant improvement in 60-day survival, along with improved oxygenation and reduced interleukin-6 levels in the treated group — a case where a trial "failed" its primary endpoint while still generating a genuine secondary signal worth reporting honestly rather than dismissing outright.

A subsequent, larger, and more rigorous trial — the TESICO trial (The Lancet Respiratory Medicine, 2023; PMID 37348523) — tested aviptadil in a broader multicenter COVID-19 respiratory failure population and found no evidence of benefit on either the primary endpoint (a 90-day ordinal outcome measure) or secondary endpoints, and additionally reported that treatment caused significant blood pressure reduction and increased vasopressor requirements in treated patients, potentially offsetting any theoretical benefit. We are reporting this negative, larger, more recent trial alongside the earlier positive-secondary-endpoint trial deliberately, since presenting only the earlier result would give an incomplete and overly favorable picture of the current evidence.

Separately, VIP has an established but smaller research base in sarcoidosis (inhaled VIP has been studied for immunoregulatory effects in this condition) and in chronic pulmonary hypertension (Leuchte HH, et al., European Respiratory Journal, 2008, studied inhaled aviptadil in 20 patients, finding a small but statistically significant pulmonary vasodilation effect). Despite this multi-decade, multi-indication research history and its orphan drug designations, VIP/aviptadil has not been approved by the FDA for any of these respiratory or pulmonary indications, and Phase 3 sarcoidosis development originally planned for 2019 was postponed in favor of the COVID-19 research program. Research-grade VIP sold here is intended exclusively for laboratory research, not for human or animal use.

VIP holds a distinction few compounds in this catalog share: a related formulation is already an approved, marketed pharmaceutical product in parts of Europe, where VIP combined with phentolamine is used as an injectable treatment for erectile dysfunction — entirely separate from its orphan-disease respiratory research applications. This means VIP's regulatory story is not simply "investigational, not yet approved" but rather "approved for one specific indication in one region, while remaining investigational for several other indications elsewhere," a nuance worth understanding before assuming a single regulatory status applies across all of VIP's research contexts.

VIP was one of the fastest peptides ever repurposed for pandemic response research: its pre-existing anti-inflammatory and antiviral nonclinical data allowed aviptadil to move into emergency compassionate-use and clinical trial programs for COVID-19 within months of the pandemic's onset, leveraging more than two decades of pre-existing human safety data from its sarcoidosis and pulmonary hypertension research history — a research advantage that entirely novel compounds, with no prior human exposure data, do not have.

VIP and PACAP are sometimes described in the research literature as a "secretin/glucagon/VIP superfamily" of structurally related peptide hormones, reflecting a shared evolutionary origin with several other well-known gut and metabolic peptide hormones, even though VIP's own research applications have moved well beyond gastrointestinal physiology into pulmonary and immunological territory.

The contrast between the 2022 U.S. trial's positive secondary signal and the 2023 TESICO trial's negative result is itself a useful case study in why single small trials, even randomized and placebo-controlled ones, can produce different conclusions from larger, more definitive follow-up studies — a pattern researchers evaluating any investigational compound's evidence base should keep in mind rather than anchoring on whichever trial they encounter first.

At Verified Peptides, we require independent third-party HPLC purity testing and mass spectrometry identity confirmation for every batch of research-grade VIP we offer, with a Certificate of Analysis (COA) available for each lot. As a 28-amino-acid peptide, VIP is larger and structurally more complex than many shorter research peptides, making rigorous synthesis verification and purity testing especially important for reproducible experimental results.

We source exclusively from manufacturers operating under Good Manufacturing Practice (GMP)-aligned quality systems, and every lot is independently verified rather than accepted solely on a supplier's internal documentation. Researchers should request and review the specific COA for their lot, checking purity percentage and confirmed molecular identity, rather than assuming consistent quality across suppliers or lots.

Because VIP research spans such varied experimental contexts — vascular, pulmonary, gastrointestinal, and immunological models — sample purity and identity verification carry outsized importance for reproducibility, since a degraded or misidentified peptide sample could plausibly confound results across any of these distinct research applications.

Lyophilized (freeze-dried) VIP is stable when stored at -20°C, protected from light and moisture, and can generally be expected to maintain integrity over extended periods in this unreconstituted form.

Once reconstituted with bacteriostatic water or an appropriate sterile diluent, VIP solution should be stored refrigerated at 2–8°C and used within the documented timeframe for that lot. As a larger peptide, VIP solutions may be somewhat more prone to degradation from repeated freeze-thaw cycling than shorter peptides, so aliquoting into single-use portions is particularly advisable to minimize unnecessary freeze-thaw exposure of any individual vial.

As with other research peptides, prolonged exposure to heat, direct light, or extended room-temperature storage will accelerate degradation and compromise structural integrity relevant to research applications. Following the lot-specific storage documentation provided with each order remains the most reliable way to preserve sample validity for experimental work.