Evidence map›Paper›PMID 39626211›Full record

ArticleJournal of medicinal chemistry2024

Discovery of Potent and Selective Pyridone-Based Small Molecule Kinetic Stabilizers of Amyloidogenic Immunoglobulin Light Chains.

Oren L Lederberg, Nicholas L Yan, Julian Sanchez, Wen Ren, Carl Ash, Steven J Wilkens, Huang Qiu, Bo Qin, Virginia H Grant, Alex B Jackman and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Oren L LederbergDepartment of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
Nicholas L YanDepartment of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
Julian SanchezDepartment of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
Wen RenDepartment of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.ORCID 0009-0001-4241-4151
Carl AshDepartment of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
Steven J WilkensProtego Biopharma, 10945 Vista Sorrento Parkway, San Diego, California 92130, United States.
Huang QiuProtego Biopharma, 10945 Vista Sorrento Parkway, San Diego, California 92130, United States.
Bo QinProtego Biopharma, 10945 Vista Sorrento Parkway, San Diego, California 92130, United States.ORCID 0000-0001-5985-6100
Virginia H GrantProtego Biopharma, 10945 Vista Sorrento Parkway, San Diego, California 92130, United States.
Alex B JackmanProtego Biopharma, 10945 Vista Sorrento Parkway, San Diego, California 92130, United States.
Robyn L StanfieldDepartment of Integrative Structural and Computational Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, United States.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, United States.
H Michael PetrassiProtego Biopharma, 10945 Vista Sorrento Parkway, San Diego, California 92130, United States.
Derek RhoadesDepartment of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.ORCID 0000-0002-9536-424X
Jeffery W KellyDepartment of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.ORCID 0000-0001-8943-3395

Funding

X-ray Scattering Technology CoreP30GM133893 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI Lin Yang · 2019 to 2026
$38.6M
Scripps Translational Science InstituteUL1TR001114 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2013 to 2017
$24.0M
ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
Probing the Proteinopathy Component of Light Chain Amyloidosis PharmacologicallyR01HL157566 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI JEFFERY W KELLY · 2021 to 2026
$3.3M
High-Speed High-Sensitivity Detector for X-ray Micro-Crystallography at GM/CA@APSS10OD012289 · OD · UNIVERSITY OF CHICAGO · PI FISCHETTI, ROBERT F. · 2014 to 2014
$2.0M
Potent and specific small molecule stabilizers of amyloidogenic antibody light chainsF31HL154732 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI YAN, NICHOLAS · 2020 to 2022
$66k
NCATS NIH HHS UL1 TR001114NHLBI NIH HHS F31 HL154732NHLBI NIH HHS R01 HL157566NIGMS NIH HHS P30 GM133893NIGMS NIH HHS R01 GM129325NIH HHS S10 OD012289
6 · The paper itself

Abstract

Kinetic stabilization of amyloidogenic immunoglobulin light chains (LCs) through small molecule binding may become the first treatment for the proteinopathy component of light chain amyloidosis (AL). Kinetic stabilizers selectively bind to the native state over the misfolding transition state, slowing denaturation. Prior λ full-length LC dimer (FL LC

Indexed as

Immunoglobulin Light ChainsPyridonesAmyloidosisCrystallography, X-RayDrug DiscoveryHumansKineticsSmall Molecule LibrariesStructure-Activity RelationshipImmunoglobulin Light ChainsPyridonesSmall Molecule Libraries

Identifiers

PMID39626211
PMCPMC12671460

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.