ArticleProceedings of the National Academy of Sciences of the United States of America2019
Stabilization of amyloidogenic immunoglobulin light chains by small molecules.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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Who cites it
41 citing papers in PubMed, 87 citations in OpenAlex.
- Small Molecule Stabilization of Diverse Amyloidogenic Immunoglobulin Light Chains Revealed by Hydrogen-Deuterium Exchange Mass Spectrometry.Journal of molecular biology · 2026Article
- When AL amyloidosis meets the liver: integrating clinical insight and current understanding.Annals of hematology · 2026Review
- Protein-Protein Interaction Stabilizers from MD Simulation-Derived Pharmacophores.Journal of chemical information and modeling · 2026Article
- Small molecule stabilization of diverse amyloidogenic immunoglobulin light chains revealed by hydrogen-deuterium exchange mass spectrometry.bioRxiv : the preprint server for biology · 2026Article
- Cooperative Free Energy: Induced Protein-Protein Interactions and Cooperative Solvation in Ternary Complexes.Journal of chemical theory and computation · 2025Article
- Investigating Local Sequence-Structural Attributes of Amyloidogenic Light Chain Variable Domains.Proteins · 2025Article
- Tracking reduction-induced molecular changes in pathological free light chains by SV-AUC.European biophysics journal : EBJ · 2025Article
- Protein Misfolding and Aggregation of Pathological IgG Light Chains in Oncohematological Dyscrasias: From Molecular Pathways to Clinical Implications.Current protein & peptide science · 2025Review
- 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
- Predicting Structural Consequences of Antibody Light Chain N-Glycosylation in AL Amyloidosis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Design and fabrication of 3D-printedJournal of applied crystallography · 2024Article
- Review
- Conformational inhibitors of protein aggregation.Current opinion in structural biology · 2023Review
- 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
- Mechanistic insights into the aggregation pathway of the patient-derived immunoglobulin light chain variable domain protein FOR005.Nature communications · 2023Article
- What Makes a Good Protein-Protein Interaction Stabilizer: Analysis and Application of the Dual-Binding Mechanism.ACS central science · 2023Article
- A constant domain mutation in a patient-derived antibody light chain reveals principles of AL amyloidosis.Communications biology · 2023Article
- Widespread amyloidogenicity potential of multiple myeloma patient-derived immunoglobulin light chains.BMC biology · 2023Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
In Ig light-chain (LC) amyloidosis (AL), the unique antibody LC protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. As a step toward developing treatments for AL patients with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, we introduce small-molecule kinetic stabilizers of the native dimeric structure of full-length LCs, which can slow or stop the amyloidogenicity cascade at its origin. A protease-coupled fluorescence polarization-based high-throughput screen was employed to identify small molecules that kinetically stabilize LCs. NMR and X-ray crystallographic data demonstrate that at least one structural family of hits bind at the LC-LC dimerization interface within full-length LCs, utilizing variable-domain residues that are highly conserved in most AL patients. Stopping the amyloidogenesis cascade at the beginning is a proven strategy to ameliorate postmitotic tissue degeneration.
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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.