Introduction

Body Protection Compound-157 (BPC-157) is a synthetic pentadecapeptide derived from a partial sequence of a protein found in human gastric juice. Over the past three decades, BPC-157 has been the subject of a substantial body of preclinical research, encompassing hundreds of published studies investigating its effects in various in vitro and animal model systems. This review provides an overview of the published literature, focusing on the molecular characterization of the peptide, key experimental findings, recognized gaps in the current evidence base, and potential future research directions.

Molecular Characterization

BPC-157 is a pentadecapeptide consisting of 15 amino acid residues with the following sequence:

Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val

• Molecular Formula: C₆₂H₉₈N₁₆O₂₂
• Molecular Weight: 1419.53 g/mol
• CAS Number: 137525-51-0
• Isoelectric Point: Approximately 4.2 (acidic peptide)

The peptide is notable for its high proline content (three consecutive proline residues), which confers structural rigidity and may contribute to resistance against enzymatic degradation. BPC-157 is freely soluble in water at physiological pH and demonstrates stability across a wide range of pH conditions, a property that is unusual among peptides of this size and composition (Sikiric et al., 1999; PMID: 10421683).

Discovery and Research History

BPC-157 research originated in the laboratory of Predrag Sikiric at the University of Zagreb, Croatia, in the early 1990s. The peptide was isolated as a fragment of BPC (Body Protection Compound), a protein identified in human gastric juice. Initial investigations focused on the observation that gastric juice appeared to contain factors with cytoprotective properties, and efforts to isolate the responsible agents led to the identification of BPC and subsequently the synthetic fragment BPC-157 (Sikiric et al., 1993; PMID: 8100806).

Since those early studies, the research group at the University of Zagreb has published extensively on BPC-157, and additional independent laboratories have contributed to the body of literature, though it should be noted that a significant proportion of published studies originate from the Zagreb group.

Summary of Key In Vitro Studies

In vitro investigations have examined BPC-157’s effects on cell cultures and isolated tissue preparations. Key findings from the published literature include:

• Endothelial cell models: Studies using human umbilical vein endothelial cells (HUVECs) have reported that BPC-157 exposure was associated with increased tube formation in Matrigel assays, a commonly used proxy for angiogenic potential. These findings have been interpreted as suggesting a role in angiogenesis-related signaling (Hsieh et al., 2017; DOI: 10.1016/j.lfs.2017.02.025).
• Fibroblast cultures: Research using tendon fibroblast cultures reported increased cell migration and proliferation rates in BPC-157-treated groups compared to controls, with proposed involvement of FAK-paxillin signaling pathways (Chang et al., 2011; PMID: 21030672).
• Nitric oxide (NO) system interactions: Several in vitro studies have investigated BPC-157’s interaction with the nitric oxide system. Published data suggest that BPC-157 may modulate NO synthase activity, though the directionality of this modulation appears to be context-dependent (Sikiric et al., 2014; DOI: 10.2174/1389201015666140922101405).
• Growth factor expression: In vitro studies have reported upregulation of vascular endothelial growth factor (VEGF) receptor expression in BPC-157-treated cell lines, with proposed downstream effects on JAK-2/STAT-3 and MAPK/ERK pathways.

Summary of Key Animal Model Studies

The majority of published BPC-157 research consists of studies conducted in rodent models. These investigations have examined the peptide’s effects across a range of experimental paradigms:

Gastrointestinal Models

Given its gastric origin, a substantial portion of BPC-157 research has focused on gastrointestinal models. Studies in rats have examined ethanol-induced gastric lesions, NSAID-induced intestinal damage, and inflammatory bowel disease models. Sikiric et al. (2006) published a comprehensive review of gastrointestinal studies, noting consistent observations of reduced lesion severity scores in BPC-157-treated animals compared to vehicle controls (DOI: 10.1016/j.lfs.2006.05.036).

Musculoskeletal Models

Several studies have investigated BPC-157 in rodent models of tendon, ligament, and muscle injury. Staresinic et al. (2003) reported observations in a rat Achilles tendon transection model, where BPC-157-treated groups demonstrated differences in biomechanical properties compared to saline-treated controls at various time points post-injury (PMID: 14600124). Krivic et al. (2006) published findings from a medial collateral ligament transection model in rats (PMID: 16451825).

Vascular Models

Research in rat models has examined BPC-157 in the context of experimentally induced vascular occlusion and thrombosis. Vukojevic et al. (2018) published findings from an abdominal aorta anastomosis model, reporting observations of vessel patency rates in BPC-157-treated versus control groups (DOI: 10.3390/molecules23010024).

Central Nervous System Models

A number of studies have examined BPC-157 in rodent models involving dopaminergic, serotonergic, and GABAergic system perturbation. Sikiric et al. (2010) reviewed published findings related to dopamine system interactions, describing observations in models of amphetamine-induced behavior, haloperidol-induced catalepsy, and experimentally-induced Parkinsonism in rats (PMID: 21187095).

Current Gaps in the Research Literature

Despite the substantial volume of published preclinical data, several significant gaps in the BPC-157 research base must be acknowledged:

• Absence of human clinical trial data: As of early 2026, no completed, peer-reviewed, Phase II or Phase III clinical trials of BPC-157 have been published in indexed journals. The peptide remains an investigational research compound without regulatory approval in any jurisdiction.
• Limited independent replication: A substantial portion of the published literature originates from a single research group. Independent replication by multiple laboratories is a cornerstone of scientific validation, and the relative scarcity of independent studies represents a meaningful limitation.
• Mechanism of action uncertainty: While multiple signaling pathways have been implicated (NO system, VEGF, FAK-paxillin, growth hormone receptors), a unified, well-characterized mechanism of action has not been established. Many proposed mechanisms are based on correlative observations rather than definitive causal experiments.
• Pharmacokinetic data deficiency: Published pharmacokinetic data for BPC-157—including absorption, distribution, metabolism, excretion (ADME) parameters, plasma half-life, and bioavailability by various routes of administration—remain extremely limited.
• Dose-response characterization: Many published studies test one or two doses rather than constructing full dose-response curves, making it difficult to establish potency or identify therapeutic windows in preclinical models.
• Long-term safety data: Chronic exposure studies with comprehensive toxicological endpoints are largely absent from the published literature.

Future Research Directions

Several avenues for future investigation have been identified in the literature:

• Rigorous independent replication of key findings from the most cited BPC-157 studies, using pre-registered protocols and appropriate statistical power analyses.
• Comprehensive pharmacokinetic profiling across species to establish ADME parameters.
• Detailed mechanism-of-action studies employing modern techniques such as proteomics, phosphoproteomics, and CRISPR-based pathway interrogation to move beyond correlative observations.
• Structure-activity relationship (SAR) studies to identify which residues are critical for observed biological activities and to develop potential analogs with improved properties.
• Formal GLP toxicology studies as a prerequisite for any future clinical development.

Conclusion

BPC-157 represents a research peptide with an extensive preclinical literature spanning more than three decades. While the published in vitro and animal model data describe a range of observations across multiple biological systems, the evidence base has notable limitations including a concentration of publications from a single group, the absence of human clinical data, and incomplete mechanistic and pharmacokinetic characterization. These gaps underscore the importance of continued, rigorous, and independent scientific investigation to determine the significance of the preclinical observations reported to date.