ATN-161

Summary

ATN‑161 (Ac‑PHSCN‑NH2) is a five‑amino‑acid peptide that antagonises integrin α5β1 (β1‑integrin) signaling. It is being investigated intravenously as an anti‑angiogenic agent in cancer, a potential inhibitor of SARS‑CoV‑2 spike‑protein binding, and a modulator of inflammatory pathways in pancreatitis and Parkinson’s disease. The compound remains investigational, with safety data from a phase‑1 oncology trial and pre‑clinical efficacy reported in animal models and in‑vitro studies.

Mechanism of Action

ATN‑161 mimics the synergy region of fibronectin and binds the extracellular domain of integrin α5β1, preventing fibronectin‑integrin interaction and downstream focal‑adhesion kinase (FAK) signaling. By blocking this pathway it can reduce angiogenesis and cell‑matrix crosstalk. In viral studies the peptide also binds the receptor‑binding domain of the SARS‑CoV‑2 spike protein, sterically hindering its attachment to integrin α5β1 and to the ACE2‑spike complex, thereby lowering viral entry.

What the Research Shows

Pre‑clinical work shows that ATN‑161 reduces caerulein‑induced acute pancreatitis in mice by blocking Spp‑1/integrin‑α5 signaling, limiting acinar‑to‑ductal metaplasia and pathological angiogenesis. In vitro docking and binding assays suggest the peptide masks the spike protein RBD, decreasing ACE2‑spike binding energy and inhibiting viral entry. A phase‑1 trial in patients with advanced solid tumours demonstrated dose‑independent pharmacokinetics, no dose‑limiting toxicities up to 16 mg kg⁻¹, and prolonged stable disease in about one‑third of participants. Review articles cite ATN‑161 as a candidate to modulate integrin‑FAK pathways in Parkinson’s disease and to counteract SARS‑CoV‑2–induced neuroinflammation, but clinical evidence for these indications is lacking.

Reported Benefits

Early human data indicate ATN‑161 is well tolerated and may produce disease‑stabilising effects in solid tumours. Animal studies suggest it can ameliorate acute pancreatitis by restoring ductal‑endothelial signaling. In vitro and computational analyses provide mechanistic support for antiviral activity against SARS‑CoV‑2. The peptide’s ability to inhibit integrin‑mediated signaling offers a rationale for exploring disease‑modifying roles in neurodegenerative and inflammatory conditions.

Limitations of the Evidence

Efficacy has only been demonstrated in pre‑clinical models for pancreatitis and viral inhibition; no clinical trials have confirmed therapeutic benefit in these areas. The oncology trial reported stable disease but no objective tumor regressions, and the study size was limited. Reviews propose broader applications (e.g., Parkinson’s disease) but cite only mechanistic rationale without human data. Overall, the evidence base remains preliminary and requires larger, controlled studies.

Safety Considerations

In the phase‑1 oncology study, ATN‑161 was administered as a 10‑minute intravenous infusion three times weekly without any dose‑limiting toxicities across doses up to 16 mg kg⁻¹. Reported adverse events were minimal, and pharmacokinetics were dose‑independent at lower doses. No safety data are provided for its use in pancreatitis, viral infection, or neurodegenerative disease, and pre‑clinical models have not reported specific toxicities. Caution is advised until further clinical safety profiling is completed.

How It Is Administered

ATN‑161 is delivered intravenously, typically as a short (≈10 min) infusion. In the published phase‑1 cancer trial the dosing schedule was three infusions per week. Formulation details beyond the peptide being supplied as an acetate‑capped, amidated molecule are not described in the abstracts.

Routes of Administration

Goals & Uses

• COVID‑19 antiviral adjunctInfectious DiseaseLow
• Fibrosis mitigationFibrotic DiseaseLow
• Glioblastoma treatmentNeuro OncologyLow
• Metastasis inhibitionOncologyModerate
• Tumor growth inhibitionOncologyModerate
• Anti-angiogenesisOncology / VascularModerate
• Anti‑angiogenesisVascularModerate
• Combination chemotherapy sensitizationOncologyLow
• Antitumor activity in solid tumorsOncologyModerate

Contraindications

• Hypersensitivity to ATN-161 or fibronectin-derived peptidesAllergyHigh
• PregnancyPopulationModeratePotential fetal risk or insufficient safety data
• Known hypersensitivity to ATN-161 or its excipientsAllergyHigh
• Active bleeding disordersHematologyModerate

Adverse Effects

• ThrombocytopeniaHematologicUncommonLow platelet count
• HeadacheNeurologicUncommonPain in the head or upper neck
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• FatigueGeneralCommonLow energy or tiredness
• Infusion‑related reaction (flushing, rash)GeneralCommon
• Elevated liver enzymesHepaticRareIncrease in AST/ALT or other hepatic markers
• Infusion-related reactionsHypersensitivityUncommon

Drug Interactions

• CarboplatinLow
• Anticoagulants / antiplatelet agentsModerate
• Anticoagulants (e.g., warfarin, heparin)Moderate
• TemozolomideLow

Population Constraints

• Severe renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative
• Pregnant or breastfeeding womenReproductiveRelative
• Severe hepatic impairmentOrgan ImpairmentRelative
• Elderly (>75 years)GeriatricRelative

Regulatory Status

• European UnionResearchNo marketing authorization; used in academic studies.
• United StatesInvestigationalIND filed; Phase I/II trials ongoing.
• United KingdomInvestigationalClinical trial approval under MHRA.

Investigational New Drug (IND) status in the United States; no marketing authorization in EU or UK.

Evidence & Sources

• Dysregulation of the Extracellular Matrix in the Synaptic Pathology of Parkinson's Disease: Molecular Mechanisms and Novel Therapeutic Approaches
  Journal ArticleModerateRubio C, et al.2026-01-01T00:00:00.000000Z
• SARS-CoV-2 mediated neuroinflammation and the impact of COVID-19 in neurological disorders
  Journal ArticleModerateAmruta N, et al.2021-01-01T00:00:00.000000Z
• Penta-peptide ATN-161 based neutralization mechanism of SARS-CoV-2 spike protein
  Journal ArticleLowRabbani G, et al.2021-01-01T00:00:00.000000Z
• ATN-161 alleviates caerulein-induced pancreatitis
  Journal ArticleLowGao RR, et al.2024-01-01T00:00:00.000000Z
• Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH(2)), a beta integrin antagonist, in patients with solid tumours
  Journal ArticleModerateCianfrocca ME, et al.2006-01-01T00:00:00.000000Z
• β1-integrin: a potential therapeutic target in the battle against cancer recurrence
  Journal ArticleModerateBarkan D, Chambers AF2011-01-01T00:00:00.000000Z

Frequently Asked Questions