ArticleImmunobiology2013
New analogs of the clinical complement inhibitor compstatin with subnanomolar affinity and enhanced pharmacokinetic properties.
Article in Immunobiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 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.
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Who cites it
93 citing papers in PubMed, 138 citations in OpenAlex.
- 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
- Inhibition of Alternative and Terminal Complement Pathway Components Modulate the Immune Response Against Bacteria and Fungi in Whole Blood.Scandinavian journal of immunology · 2025Article
- Reconstitution of the alternative pathway of the complement system enables rapid delineation of the mechanism of action of novel inhibitors.The Journal of biological chemistry · 2024Article
- Praziquantel and factor H recruitment differentially affect the susceptibility ofFrontiers in immunology · 2024Article
- The function of the complement system remains fully intact throughout the course of allogeneic stem cell transplantation.Frontiers in immunology · 2024Article
- Complement System Inhibitory Drugs in a Zebrafish (International journal of molecular sciences · 2023Article
- The Complement-Targeted Inhibitor Mini-FH Protects against Experimental Periodontitis via Both C3-Dependent and C3-Independent Mechanisms.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Article
- Inflammation-Controlled Anti-Inflammatory Hydrogels.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Complement inhibition can decrease the haemostatic response in a microvascular bleeding model at multiple levels.Frontiers in immunology · 2023Article
- The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target.Immunological reviews · 2023Review
- Article
- A Clinical and Preclinical Assessment of Clinical Trials for Dry Age-Related Macular Degeneration.Ophthalmology science · 2022Review
- Insight into mode-of-action and structural determinants of the compstatin family of clinical complement inhibitors.Nature communications · 2022Article
- Complement C3 inhibition in severe COVID-19 using compstatin AMY-101.Science advances · 2022Article
- Compstatins: the dawn of clinical C3-targeted complement inhibition.Trends in pharmacological sciences · 2022Review
- Anti-Inflammatory and Anti-Rheumatic Potential of Selective Plant Compounds by Targeting TLR-4/AP-1 Signaling: A Comprehensive Molecular Docking and Simulation Approaches.Molecules (Basel, Switzerland) · 2022Article
- Structure-function analysis for the development of peptide inhibitors for a Gram-positive quorum sensing system.Molecular microbiology · 2022Article
- Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Therapeutic modulation of the complement system has become increasingly important in line with the growing recognition of the role of complement in numerous diseases. Compstatin, a peptidic inhibitor that acts at the central level of the complement cascade, is currently in clinical evaluation but routes to improve its efficacy have not yet been fully explored. Here, we report improvements in both the inhibitory potency and pharmacokinetic parameters of compstatin that broaden its clinical applications. Selective modification of the compstatin N-terminus with non-proteinogenic amino acids resulted in the first analogue with subnanomolar binding affinity (KD=0.5nM) and other similarly potent derivatives with improved solubility in clinically relevant solvents. Detailed structure-activity relationship studies based on biophysical and computational methods revealed key structural determinants for the observed improvements. Importantly, pharmacokinetic evaluation in non-human primates revealed target-driven elimination kinetics with plasma half-life values exceeding expectations for peptidic drugs (close to 12h). This successful optimization strategy is expected to pave the way for systemic administration of compstatin in a range of clinical conditions.
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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.