ArticleJournal of medicinal chemistry2021
Discovery of Potent Coumarin-Based Kinetic Stabilizers of Amyloidogenic Immunoglobulin Light Chains Using Structure-Based Design.
Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Small Molecule Stabilization of Diverse Amyloidogenic Immunoglobulin Light Chains Revealed by Hydrogen-Deuterium Exchange Mass Spectrometry.Journal of molecular biology · 2026Article
- Small molecule stabilization of diverse amyloidogenic immunoglobulin light chains revealed by hydrogen-deuterium exchange mass spectrometry.bioRxiv : the preprint server for biology · 2026Article
- Performance and comparison of FLCCheck: a novel serum free light chain assay for the Auxiliary Diagnosis of Multiple Myeloma.European journal of medical research · 2025Article
- Discovery of Potent and Selective Pyridone-Based Small Molecule Kinetic Stabilizers of Amyloidogenic Immunoglobulin Light Chains.Journal of medicinal chemistry · 2024Article
- Conformational Differences in the Light Chain Constant Domain of Immunoglobulin G and Free Light Chain May Influence Proteolysis in AL Amyloidosis.Journal of molecular biology · 2024Article
- Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.Molecular neurodegeneration · 2024Review
- Crystal Structures of Diaryl Hydrazone and Sulfone Stabilizers in Complex with an Amyloidogenic Light Chain Reveal an Alternate Ligand-Binding Cavity.Israel journal of chemistry · 2023Article
- Pharmacological stabilization of the native state of full-length immunoglobulin light chains to treat light chain amyloidosis.Current opinion in chemical biology · 2023Review
- A constant domain mutation in a patient-derived antibody light chain reveals principles of AL amyloidosis.Communications biology · 2023Article
- Design, Catalyst-Free Synthesis of New Novel α-Trifluoromethylated Tertiary Alcohols Bearing Coumarins as Potential Antifungal Agents.Molecules (Basel, Switzerland) · 2022Article
- Amyloidogenic immunoglobulin light chain kinetic stabilizers comprising a simple urea linker module reveal a novel binding sub-site.Bioorganic & medicinal chemistry letters · 2022Article
- Article
- Barriers to Small Molecule Drug Discovery for Systemic Amyloidosis.Molecules (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
In immunoglobulin light-chain (LC) amyloidosis, transient unfolding or unfolding and proteolysis enable aggregation of LC proteins, causing potentially fatal organ damage. A drug that kinetically stabilizes LCs could suppress aggregation; however, LC sequences are variable and have no natural ligands, hindering drug development efforts. We previously identified high-throughput screening hits that bind to a site at the interface between the two variable domains of the LC homodimer. We hypothesized that extending the stabilizers beyond this initially characterized binding site would improve affinity. Here, using protease sensitivity assays, we identified stabilizers that can be divided into four substructures. Some stabilizers exhibit nanomolar EC
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