ArticleThe Journal of biological chemistry2012
A small-molecule screen yields idiotype-specific blockers of neuromyelitis optica immunoglobulin G binding to aquaporin-4.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Monoclonal Antibody-Based Treatments for Neuromyelitis Optica Spectrum Disorders: From Bench to Bedside.Neuroscience bulletin · 2020Review
- Elevated Plasma Chemokines for Eosinophils in Neuromyelitis Optica Spectrum Disorders during Remission.Frontiers in neurology · 2018Article
- Experimental models of neuromyelitis optica: current status, challenges and future directions.Neuroscience bulletin · 2015Review
- Treatment of neuromyelitis optica: state-of-the-art and emerging therapies.Nature reviews. Neurology · 2014Review
- Neuromyelitis optica: clinical features, immunopathogenesis and treatment.Clinical and experimental immunology · 2014Review
- Biology of AQP4 and anti-AQP4 antibody: therapeutic implications for NMO.Brain pathology (Zurich, Switzerland) · 2013Review
- Immunology of neuromyelitis optica: a T cell-B cell collaboration.Annals of the New York Academy of Sciences · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system caused by binding of anti-aquaporin-4 (AQP4) autoantibodies (NMO-IgG) to AQP4 on astrocytes. A screen was developed to identify inhibitors of NMO-IgG-dependent, complement-dependent cytotoxicity. Screening of 50,000 synthetic small molecules was done using CHO cells expressing human AQP4 and a human NMO recombinant monoclonal antibody (rAb-53). The screen yielded pyrano[2,3-c]pyrazoles that blocked rAb-53 binding to AQP4 and prevented cytotoxicity in cell culture and spinal cord slice models of NMO. Structure-activity analysis of 82 analogs yielded a blocker with IC(50) ∼ 6 μm. Analysis of the blocker mechanism indicated idiotype specificity, as (i) pyrano[2,3-c]pyrazoles did not prevent AQP4 binding or cytotoxicity of other NMO-IgGs, and (ii) surface plasmon resonance showed specific rAb-53 binding. Antibody structure modeling and docking suggested a putative binding site near the complementarity-determining regions. Small molecules with idiotype-specific antibody targeting may be useful as research tools and therapeutics.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.