Eptifibatide: Integrilin blood-clot preventer for heart attacks
A lab-made drug, modeled on a protein in rattlesnake venom, that stops blood platelets from clumping into dangerous clots during heart attacks or procedures to open blocked heart arteries. FDA-approved.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
Eptifibatide (brand name Integrilin) is an intravenous antiplatelet drug given in hospital during acute coronary syndromes — heart attacks and unstable angina — and during percutaneous coronary intervention (PCI), the catheter procedure used to open blocked heart arteries. It is a small synthetic peptide modeled on a protein found in the venom of the southeastern pygmy rattlesnake (Sistrurus miliarius barbouri), and it works by blocking the final common step that lets platelets clump into a clot (Scarborough 1991, J Biol Chem). The molecule is a cyclic heptapeptide containing a disulfide bridge and non-standard residues, so the 12-letter raw sequence shown above is an approximation rather than the true chemical structure — the active drug is a constrained ring, not a linear chain (Phillips 1997; Scarborough 1999).
History
Eptifibatide's story begins with snake venom. In 1991, Scarborough and colleagues isolated barbourin, a small protein from the venom of Sistrurus m. barbouri that bound selectively to the platelet integrin glycoprotein IIb/IIIa (Scarborough 1991, J Biol Chem). Barbourin's selectivity — over closely related integrins — made it an unusually clean lead, and medicinal chemists at COR Therapeutics used its key recognition motif to design a small, stable, cyclic peptide drug candidate. The development program, summarized later by Scarborough himself (Scarborough 1999, Am Heart J), produced eptifibatide, and the drug was tested through the PURSUIT trial in acute coronary syndromes (Harrington 1997, Am J Cardiol; PURSUIT investigators 1998, NEJM) and the ESPRIT trial in coronary stenting (ESPRIT investigators 2000, Lancet). It was marketed as Integrilin and entered routine catheterization-lab use in the late 1990s and 2000s.
What it does
Eptifibatide blocks the glycoprotein IIb/IIIa receptor on the surface of platelets. GPIIb/IIIa is the receptor platelets use to grab fibrinogen and von Willebrand factor and stick to one another — it is the final common pathway of platelet aggregation, regardless of what activated the platelet in the first place (Tcheng 2002, Expert Opin Pharmacother; Zeymer 2007, Cardiovasc Drug Rev). By occupying this receptor, eptifibatide stops platelets from cross-linking into the thrombus that obstructs a coronary artery during a heart attack or after stent placement. Compared with other GPIIb/IIIa inhibitors, eptifibatide is highly selective for the receptor and dissociates rapidly when the infusion is stopped, so platelet function returns toward normal within hours (Zeymer 2007; Phillips 1997).
Mechanism
GPIIb/IIIa (integrin αIIbβ3) is the most abundant integrin on the platelet surface. It recognises an RGD- or KGD-tripeptide motif in fibrinogen, von Willebrand factor, fibronectin, and vitronectin, and uses those ligands as cross-links to glue activated platelets together. Eptifibatide is a competitive, reversible antagonist that occupies the same fibrinogen-binding pocket via a constrained KGD pharmacophore carried on a cyclic heptapeptide ring closed by an intramolecular disulfide bridge; the cyclic backbone mimics the receptor-binding loop of the parent disintegrin barbourin (Scarborough 1991, J Biol Chem; Tcheng 2002, Expert Opin Pharmacother). Pharmacokinetically, the drug reaches near-maximal platelet inhibition within minutes of an intravenous bolus, has a short plasma half-life, and is cleared predominantly by the kidneys, which is why renal function constrains its use (Phillips 1997, Am J Cardiol; Gilchrist 2003, Clin Pharmacokinet). On-treatment receptor occupancy of platelet GPIIb/IIIa achieved with eptifibatide has been measured directly and is broadly comparable to that of the small-molecule antagonist tirofiban at standard PCI dosing (Puri 2013, Indian Heart J).
Evidence
- Human: Tested in two pivotal randomized trials. PURSUIT (~10,948 patients with non-ST-elevation acute coronary syndromes) showed that eptifibatide reduced the composite of death or myocardial infarction at 30 days versus placebo (PURSUIT investigators 1998, NEJM). ESPRIT (2,064 patients undergoing elective coronary stenting) showed a reduction in 48-hour death, MI, and urgent target-vessel revascularization (ESPRIT investigators 2000, Lancet). Subsequent analyses of these trials examined subgroups including patients with chronic kidney disease (Reddan 2003, Am J Cardiol) and current smokers (Hasdai 2000, Am Heart J), and an ESPRIT substudy reported improved coronary flow reserve after stenting (Gibson 2001, Am J Cardiol). More recent registration trials extended use into ischemic stroke: the MOST trial reported that adjunctive intravenous eptifibatide (or argatroban) given with thrombolysis did not improve outcomes versus thrombolysis alone in acute ischemic stroke (Adeoye 2024, NEJM), and a preplanned cohort analysis in patients undergoing mechanical thrombectomy reached a similar conclusion (Rines 2025, JAMA Neurology).
- In vitro: Eptifibatide is a high-affinity, highly selective GPIIb/IIIa antagonist (Phillips 1997, Am J Cardiol). In whole-blood studies it inhibits fibrinogen-mediated aggregation but has also been reported to potentiate platelet–leukocyte interactions and tissue-factor expression following platelet activation, a complexity that has been discussed as a possible explanation for some clinical observations (Scholz 2002, Platelets).
Known effects
- Reduces death and MI in non-ST-elevation acute coronary syndromes — Phase III, FDA-approved indication (PURSUIT 1998, NEJM).
- Reduces ischemic complications of coronary stenting — Phase III, FDA-approved indication (ESPRIT 2000, Lancet; O'Shea 2001, JAMA).
- Comparable receptor occupancy to tirofiban in head-to-head measurement during PCI (Puri 2013, Indian Heart J).
- No benefit in adjunctive use for acute ischemic stroke — Phase III, recent negative trial (Adeoye 2024, NEJM; Rines 2025, JAMA Neurology).
Safety signals
Bleeding is the dominant safety issue with all GPIIb/IIIa inhibitors. Across the eptifibatide trial program, bleeding events — including major bleeding and access-site bleeding around the femoral arterial sheath used for PCI — were the most frequently reported adverse effects (PURSUIT 1998, NEJM; ESPRIT 2000, Lancet; Curran 2005, Drugs). Eptifibatide is renally cleared, and renal-function-aware dosing matters: a single-center study found that computerized dose adjustment was associated with lower bleeding and mortality rates compared with historical practice (Putney 2009, Am Heart J). A separate pharmacokinetic study reported that obesity alters eptifibatide exposure, with implications for how reliably standard weight-based dosing achieves the intended platelet inhibition (Vavalle 2011, Am Heart J).
Regulatory status
- US: Prescription-only, intravenous. FDA-approved in 1998 as Integrilin for acute coronary syndromes, with the labelled indication expanded to patients undergoing PCI. Generic eptifibatide remains available.
- EU: Approved in the European Union for the same indications; an economic analysis of European PURSUIT-trial patients is published (Brown 2002, Eur Heart J). The originator brand Integrilin was discontinued by its manufacturer for commercial reasons (manufacturing ceased in late 2023; the originator EU marketing authorisation was formally withdrawn in 2026). Generic eptifibatide products remain authorised and marketed in the EU.
- Use setting: Hospital-administered intravenous infusion in the cardiac catheterization laboratory or coronary care unit. Not a self-administered drug.
Related peptides
- Barbourin — the parent disintegrin from Sistrurus m. barbouri venom from which eptifibatide was designed (Scarborough 1991, J Biol Chem).
- Tirofiban — a non-peptide GPIIb/IIIa antagonist in the same drug class, used in similar clinical settings; head-to-head pharmacodynamic comparison in PCI patients reported by Puri (2013, Indian Heart J).
- Abciximab — a monoclonal-antibody Fab GPIIb/IIIa inhibitor in the same drug class, distinguished by much slower receptor dissociation kinetics than eptifibatide (Zeymer 2007, Cardiovasc Drug Rev).
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Could the same peptide that stops heart clots be used to carry cancer drugs to tumors that recruit platelets?
If this worked, doctors could reuse a well-known hospital drug as a tumor-homing delivery tool, potentially making cancer treatments more precise and reducing side effects for patients.
Could eptifibatide help heart attack patients not just by stopping clots, but also by calming an overactive immune response in their arteries?
If true, it would mean this existing hospital drug has a hidden second benefit during heart attacks, and might even be useful in other conditions where harmful immune traps damage blood vessels.
▸3-letter notation
▸citationbibtex
@peptide{pep04433,
sequence = {MPRCHPCNGDGD},
target = {},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}