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A 58-residue protein from cow lungs that became one of the most studied — and most argued-over — drugs in cardiac surgery.
Also known as: BPTI · bovine pancreatic trypsin inhibitor · Trasylol · Antilysine
Part of the Foundational & therapeutic peptides cluster
Overview
Aprotinin is a 58-amino-acid Kunitz-type serine protease inhibitor isolated from bovine lung, identical to bovine pancreatic trypsin inhibitor (BPTI). By inhibiting plasmin and kallikrein it reduces fibrinolysis and bleeding, and it was FDA-approved in 1993 for cardiac surgery — cutting blood-product exposures from 5.7 to 2.2 per patient in one trial — before being withdrawn from the US market in 2008 after a Canadian trial raised mortality and kidney concerns that were later disputed.
Source & context
Biological / chemical source: Isolated from bovine lung tissue (a natural polypeptide, not synthetic)
Primary research or clinical context: Approved (US FDA, 1993) as an antifibrinolytic to reduce bleeding and transfusion in cardiac surgery; withdrawn from the US market in 2008 over safety questions, later re-examined
What aprotinin is
Aprotinin is a 58-residue polypeptide purified from bovine lung — chemically the same molecule as bovine pancreatic trypsin inhibitor (BPTI), the textbook example of a Kunitz-type protease inhibitor and one of the first proteins whose folding was studied in detail. As a drug it is a broad, nonspecific serine protease inhibitor with particular activity against plasmin, trypsin, chymotrypsin and kallikrein (Smith et al., International Journal of Clinical Practice 2010). The FDA approved it in 1993 to reduce bleeding and transfusion requirements during cardiac surgery, where it was used mainly in complex and repeat operations (IUPHAR record; Deanda & Spiess, Journal of Thoracic and Cardiovascular Surgery 2012).
Sequence and structure
The IUPHAR record gives the full sequence, RPDFCLEPPYTGPCKARIIRYFYNAKAGLCQTFVYGGCRAKRNNFKSAEDCMRTCGGA, displayed as chips above. At 58 residues and about 6.5 kDa it sits at the boundary between peptide and small protein, and its six cysteines pair into three disulfide bonds that make the Kunitz fold exceptionally stable — the reason BPTI could be crystallised, sequenced and used as a model system decades ago. The reactive-site lysine at position 15 inserts into the active site of trypsin-like proteases and inhibits them competitively.
Mechanism in cardiac surgery
Cardiopulmonary bypass massively activates the plasma contact system on first passage through the circuit, generating thrombin, activating platelets and impairing their adhesive receptors. Aprotinin was first used to inhibit plasmin-induced complement activation; the reduction in blood loss was noticed by chance, and later work attributed it to protection of the platelet adhesive receptor GpIb at the onset of bypass (Westaby, Annals of Thoracic Surgery 1993). It has no effect on platelet aggregation induced by most agonists but inhibits thrombin-induced platelet activation, which bears on the long-running question of whether it is prothrombotic (Poullis et al., Perfusion 2001).
Clinical evidence
A US multicentre, randomised, double-blind trial gave high-dose aprotinin or placebo to 216 patients undergoing coronary bypass grafting. In primary operations, total blood-product exposures were 2.2 per patient with aprotinin versus 5.7 with placebo; in repeat operations, 0.3 versus 10.7. Mortality was 5.6% versus 3.7%, a difference that was not statistically significant, and early vein-graft patency was assessed by ultrafast CT (Lemmer et al., Journal of Thoracic and Cardiovascular Surgery 1994). Its use in severe acute pancreatitis, studied for 50 years, has been disappointing, arguably because trials never achieved adequate plasma and peritoneal levels (Smith et al. 2010).
| Surgery | Aprotinin | Placebo |
|---|---|---|
| Primary coronary bypass | 2.2 | 5.7 |
| Repeat coronary bypass | 0.3 | 10.7 |
The 2008 withdrawal and its aftermath
In 2008 aprotinin was withdrawn from the US market after preliminary results from a large randomised Canadian trial raised questions — previously aired in observational studies — about increased mortality and renal failure after cardiac surgery. A subsequent re-review of the Canadian data identified flaws in the study and in the interpretation of its results, and the controversy has been revisited in the surgical literature since (Deanda & Spiess 2012). The evidence for this profile does not document a formal US re-approval; regulatory status should be checked with the relevant authority.
Newer directions
Because aprotinin inhibits host proteases that some viruses need to process their surface proteins, it was reported in 2020 to inhibit SARS-CoV-2 replication in cell culture (Bojkova et al., Cells 2020). As of the September 2026 snapshot, ClinicalTrials.gov lists a recruiting phase 3 trial of aprotinin in acute respiratory distress syndrome alongside older surgical studies.
Relation to other peptides on this site
Aprotinin is the directory's clearest example of a natural inhibitor polypeptide: it neither mimics a hormone nor binds a receptor, but jams enzymes. Desirudin, the recombinant leech thrombin inhibitor, is its closest therapeutic relative — a natural anticoagulant polypeptide of similar size with the opposite effect on clotting. Ziconotide and other disulfide-rich toxin-derived peptides share its structural logic of a small, cystine-knotted fold.
Sequence
One-letter sequence commonly cited for Aprotinin (educational; isoforms and modifications may differ):
RPDFCLEPPYTGPCKARIIRYFYNAKAGLCQTFVYGGCRAKRNNFKSAEDCMRTCGGA
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
- 58-residue single-chain polypeptide, the classic Kunitz-domain protease inhibitor (BPTI), stabilised by three disulfide bonds
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C284H432N84O79S7
- Average reference mass
- ≈ 6,511
- Receptors
- No receptor — a competitive inhibitor of serine proteases including plasmin, trypsin, chymotrypsin and kallikrein
- Backbone
- 58-residue single-chain polypeptide, the classic Kunitz-domain protease inhibitor (BPTI), stabilised by three disulfide bonds
- Status
- Approved: US FDA, 1993 (reduction of perioperative blood loss in cardiac surgery). Withdrawn from the US market in 2008; a 2026 phase 3 trial in ARDS is recruiting
- PubChem CID: 16130295
- IUPHAR ligand: 6570
- DrugBank: DB06692
- CAS RN: 9087-70-1
- UNII: 04XPW8C0FL
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 33 registered studies with “Aprotinin” as an intervention (snapshot 2026-09-07). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07317050 | Clinical Trial With Aprotinin in the Acute Respiratory Distress Syndrome Treatment | Phase 3 | recruiting | 2026-07-15 |
| NCT03189355 | Expression of Protein Tyrosine Phosphatase 1B (PTP1B) and Body Composition Modification in Patients With Septi | Not applicable | completed | 2026-02-06 |
| NCT07337707 | New Microbiota-endocrine Axis in Fructose Malabsorption-caused Visceral Hypersensitivity in Irritable Bowel Sy | Not applicable | not yet recruiting | 2026-01-13 |
| NCT04602689 | Fibrin Glue After ESD for High Risk Patients of Bleeding | Not applicable | completed | 2024-11-29 |
| NCT06328049 | A Study of Trilaciclib Combined With Chemotherapy in the Treatment of NSCLC | Phase 2 | unknown | 2024-03-25 |
| NCT05490940 | Sensory Recovery of Digital Nerves After Microsurgical Epineural Neurorrhaphy Alone or in Combination With Tis | Not applicable | unknown | 2023-03-03 |
Aprotinin — 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: 58-residue single-chain polypeptide, the classic Kunitz-domain protease inhibitor (BPTI), stabilised by three disulfide bondsAverage reference mass: 6,511 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.
- IdentifiersCross-linked to IUPHAR ligand 6570 and PubChem CID 16130295.
- TrialsClinicalTrials.gov snapshot added: 33 registered studies, highest phase 4.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Aprotinin
What is Aprotinin?+
Aprotinin is a 58-amino-acid Kunitz-type serine protease inhibitor isolated from bovine lung, identical to bovine pancreatic trypsin inhibitor (BPTI). By inhibiting plasmin and kallikrein it reduces fibrinolysis and bleeding, and it was FDA-approved in 1993 for cardiac surgery — cutting blood-product exposures from 5.7 to 2.2 per patient in one trial — before being withdrawn from the US market in 2008 after a Canadian trial raised mortality and kidney concerns that were later disputed.
What Canadian product status is recorded for Aprotinin?+
Canadian product status for Aprotinin 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 Aprotinin?+
Aprotinin is commonly described as approximately 58 amino acids (Kunitz-type serine protease inhibitor).
What is aprotinin?+
A 58-amino-acid serine protease inhibitor from bovine lung (identical to BPTI) that reduces fibrinolysis and surgical bleeding. FDA-approved in 1993 for cardiac surgery and withdrawn from the US market in 2008.
Why was aprotinin withdrawn?+
Preliminary results from a large Canadian randomised trial in 2008 suggested increased mortality and renal failure after cardiac surgery. A later re-review found flaws in that study and its interpretation.
How much did aprotinin reduce transfusion?+
In a 1994 US trial, blood-product exposures fell from 5.7 to 2.2 per patient in primary coronary bypass and from 10.7 to 0.3 in repeat operations.
What is the sequence of aprotinin?+
RPDFCLEPPYTGPCKARIIRYFYNAKAGLCQTFVYGGCRAKRNNFKSAEDCMRTCGGA — 58 residues with three disulfide bonds, the classic Kunitz fold.
Is aprotinin still being studied?+
Yes. A phase 3 trial in acute respiratory distress syndrome is recruiting as of 2026, following 2020 cell-culture work showing inhibition of SARS-CoV-2 replication.
Related peptides
References & further reading
- 1.Lemmer JH Jr et al. (1994). Aprotinin for coronary bypass operations: efficacy, safety, and influence on early saphenous vein graft patency. Journal of Thoracic and Cardiovascular Surgery
- 2.Deanda A Jr & Spiess BD (2012). Aprotinin revisited. Journal of Thoracic and Cardiovascular Surgery
- 3.Westaby S (1993). Aprotinin in perspective. Annals of Thoracic Surgery
- 4.Poullis M et al. (2001). Aprotinin: is it prothrombotic? Perfusion
- 5.Smith M et al. (2010). Aprotinin in severe acute pancreatitis. International Journal of Clinical Practice
- 6.Bojkova D et al. (2020). Aprotinin Inhibits SARS-CoV-2 Replication. Cells
- 7.PubChem — Aprotinin (CID 16130295)