ArticleNature communications2022
Insight into mode-of-action and structural determinants of the compstatin family of clinical complement inhibitors.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Longitudinal multiomics profiling of extracorporeal cross-circulation with pig liver xenografts in human decedents.Nature medicine · 2026Article
- Peptide-Based Delivery Systems: Selected Insights into Cell-Penetrating Peptides.ACS chemical neuroscience · 2026Review
- Bioorthogonal tuning of nanosurface opsonisationChemical communications (Cambridge, England) · 2026Article
- Microglial checkpoint collapse in Alzheimer's disease: a tri-axial framework for biomarker-informed neuroimmune therapy.Journal of neuroinflammation · 2026Review
- From the Proteome to Therapeutics: A Multi-Database Approach to Drug Discovery in Periodontitis-An Exploratory Pilot Study.Journal of clinical periodontology · 2026Article
- New Analogs of the Compstatin Family of Clinical Complement Inhibitors with Low Picomolar Target Affinity.Journal of medicinal chemistry · 2026Article
- Advances in cryo-EM that have shaped mechanistic models of membrane-attack-complex assembly and regulation.IUCrJ · 2026Review
- Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging.Nature aging · 2026Article
- Complement Dysregulation in Kidney Diseases: Mechanisms, Biomarkers, and Emerging Targeted Therapies.International journal of molecular sciences · 2026Review
- Complement C3 recognition by C3 convertases.Science advances · 2026Article
- Major bioactive metabolites derived fromFrontiers in pharmacology · 2026Review
- Structural insights into C3 convertase activity of the classical pathway of complement.Nature communications · 2025Article
- Proteolytic profiling of human plasma reveals an immunoactive complement C3 fragment.The EMBO journal · 2025Article
- Enhanced immunocompatibility and hemocompatibility of nanomedicines across multiple species using complement pathway inhibitors.Science advances · 2025Article
- Differential effects of C5 inhibition, C3 inhibition, and alternative pathway inhibition on bacterial killing in vitro.Blood advances · 2025Article
- Determining Ligand Binding and Specificity Within the βBiomolecules · 2025Article
- Complement-targeted therapeutics: Are we there yet, or just getting started?European journal of immunology · 2024Review
- Navigating the Complement Pathway to Optimize PNH Treatment with Pegcetacoplan and Other Currently Approved Complement Inhibitors.International journal of molecular sciences · 2024Review
- CG001, a C3b-targeted complement inhibitor, blocks 3 complement pathways: development and preclinical evaluation.Blood advances · 2024Article
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 4 countries.
Funding
Abstract
With the addition of the compstatin-based complement C3 inhibitor pegcetacoplan, another class of complement targeted therapeutics have recently been approved. Moreover, compstatin derivatives with enhanced pharmacodynamic and pharmacokinetic profiles are in clinical development (e.g., Cp40/AMY-101). Despite this progress, the target binding and inhibitory modes of the compstatin family remain incompletely described. Here, we present the crystal structure of Cp40 complexed with its target C3b at 2.0-Å resolution. Structure-activity-relationship studies rationalize the picomolar affinity and long target residence achieved by lead optimization, and reveal a role for structural water in inhibitor binding. We provide explanations for the narrow species specificity of this drug class and demonstrate distinct target selection modes between clinical compstatin derivatives. Functional studies provide further insight into physiological complement activation and corroborate the mechanism of its compstatin-mediated inhibition. Our study may thereby guide the application of existing and development of next-generation compstatin analogs.
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What Socratic holds
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 Socratic graph.