ArticleBlood2014
Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03316521 (Safety, Tolerability, Pharmacokinetics), which is not on this map. Cited by 111 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of a Single Ascending Dose (SAD) and a Multiple Dose (MD) of the Complement Inhibitor AMY-101. A Prospective, Single-center, Open-label, First-In-Human (FIH) Clinical Study in Healthy Male Volunteers
Who cites it
111 citing papers in PubMed, 194 citations in OpenAlex.
- Trial
- Complement C3 inhibitory peptide AMY-101 ameliorates brain injury in a mouse model of NMOSD.Annals of medicine · 2026Article
- New Analogs of the Compstatin Family of Clinical Complement Inhibitors with Low Picomolar Target Affinity.Journal of medicinal chemistry · 2026Article
- A second generation of C3 humanized rats for preclinical evaluation of human C3 inhibitors.Blood vessels, thrombosis & hemostasis · 2026Article
- Isoniazid subverting erythrocyte homeostasis: implications for tuberculosis therapy.Frontiers in pharmacology · 2026Article
- Efficacy analysis of iptacopan in a patient with thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation: a case report.Frontiers in immunology · 2026Article
- Redox Regulation of Complement Pathway Activation in Aging and Related Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Complement C3 in panvascular disease: a central integrator of immune signaling and vascular remodeling.Clinical science (London, England : 1979) · 2025Review
- Diffuse Large B-Cell Lymphoma Combined With Paroxysmal Nocturnal Hemoglobinuria: A Rare Case Report.Clinical case reports · 2025Article
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- Article
- Monocyte uptake of polymeric peptidoglycan is bimodal and governed by complement C3 and C4 opsonins.JCI insight · 2024Article
- Navigating the Complement Pathway to Optimize PNH Treatment with Pegcetacoplan and Other Currently Approved Complement Inhibitors.International journal of molecular sciences · 2024Review
- A novel complement C3 inhibitor CP40-KK protects against experimental pulmonary arterial hypertension via an inflammasome NLRP3 associated pathway.Journal of translational medicine · 2024Article
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
- Complement System Inhibitory Drugs in a Zebrafish (International journal of molecular sciences · 2023Article
- SAR443809: a selective inhibitor of the complement alternative pathway, targeting complement factor Bb.Blood advances · 2023Article
- Novel targeted C3 inhibitor pegcetacoplan for paroxysmal nocturnal hemoglobinuria.Clinical and experimental medicine · 2023Review
- The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target.Immunological reviews · 2023Review
- Cold AIHA and the best treatment strategies.Hematology. American Society of Hematology. Education Program · 2022Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated intravascular hemolysis due to the lack of CD55 and CD59 on affected erythrocytes. The anti-C5 antibody eculizumab has proven clinically effective, but uncontrolled C3 activation due to CD55 absence may result in opsonization of erythrocytes, possibly leading to clinically meaningful extravascular hemolysis. We investigated the effect of the peptidic C3 inhibitor, compstatin Cp40, and its long-acting form (polyethylene glycol [PEG]-Cp40) on hemolysis and opsonization of PNH erythrocytes in an established in vitro system. Both compounds demonstrated dose-dependent inhibition of hemolysis with IC50 ∼4 µM and full inhibition at 6 µM. Protective levels of either Cp40 or PEG-Cp40 also efficiently prevented deposition of C3 fragments on PNH erythrocytes. We further explored the potential of both inhibitors for systemic administration and performed pharmacokinetic evaluation in nonhuman primates. A single intravenous injection of PEG-Cp40 resulted in a prolonged elimination half-life of >5 days but may potentially affect the plasma levels of C3. Despite faster elimination kinetics, saturating inhibitor concentration could be reached with unmodified Cp40 through repetitive subcutaneous administration. In conclusion, peptide inhibitors of C3 activation effectively prevent hemolysis and C3 opsonization of PNH erythrocytes, and are excellent, and potentially cost-effective, candidates for further clinical investigation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.