Evidence map›Paper›PMID 35767437›Full record

ArticleJournal of medicinal chemistry2022

Next-Generation Diprovocims with Potent Human and Murine TLR1/TLR2 Agonist Activity That Activate the Innate and Adaptive Immune Response.

Ming-Hsiu Yang, Jamie L Russell, Yuto Mifune, Ying Wang, Hexin Shi, Eva Marie Y Moresco, Daniel J Siegwart, Bruce Beutler, Dale L Boger

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 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

9 authors.

Ming-Hsiu YangDepartment of Chemistry and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, United States.
Jamie L RussellCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Yuto MifuneDepartment of Chemistry and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, United States.
Ying WangCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Hexin ShiCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Eva Marie Y MorescoCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Daniel J SiegwartDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.ORCID 0000-0003-3823-1931
Bruce BeutlerCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Dale L BogerDepartment of Chemistry and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, United States.ORCID 0000-0002-3966-3317

Funding

Systems Biology CoreU19AI100627 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ULEVITCH, RICHARD J · 2012 to 2021
$49.1M
Automated Forward Genetic Analysis of Adaptive ImmunityR01AI125581 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI BRUCE A BEUTLER · 2016 to 2026
$19.5M
ANTITUMORE ANTIBIOTICS: STREPTONIGRIN AND LAVENDAMYCINR01CA042056 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI BOGER, DALE L · 1985 to 2024
$10.6M
Discovery and Analysis of Synthetic TLR Agonists and AntagonistsU24AI082657 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BEUTLER, BRUCE A, BOGER, DALE L · 2009 to 2013
$3.8M
Defining the molecular interactions within nanoparticles that enable delivery of long nucleic acidsR01EB025192 · NIBIB · UT SOUTHWESTERN MEDICAL CENTER · PI SIEGWART, DANIEL JOHN · 2018 to 2025
$3.1M
Multiplexed nanoparticle delivery to increase CRISPR/Cas gene editing for enhanced cancer therapyR01CA269787 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Daniel John Siegwart · 2022 to 2026
$1.9M
NCI NIH HHS R01 CA042056NCI NIH HHS R01 CA269787NIAID NIH HHS R01 AI125581NIAID NIH HHS U19 AI100627NIAID NIH HHS U24 AI082657NIBIB NIH HHS R01 EB025192
6 · The paper itself

Abstract

The diprovocims, a new class of toll-like receptor (TLR) agonists, bear no similarity to prior TLR agonists, act through a well-defined mechanism (TLR1/TLR2 agonist), exhibit exquisite structure-activity relationships, and display in vivo adjuvant activity. They possess potent and efficacious agonist activity toward human TLR1/TLR2 but modest agonism toward the murine receptor. A manner by which diprovocims can be functionalized without impacting hTLR1/TLR2 activity is detailed, permitting future linkage to antigenic, targeting, or delivery moieties. Improvements in both potency and its low efficacy in the murine system were also achieved, permitting more effective use in animal models while maintaining the hTLR1/TLR2 activity. The prototypical member diprovocim-X exhibits the excellent potency/efficacy of diprovocim-1 in human cells, displays substantially improved potency/efficacy in mouse macrophages, and serves as an adjuvant in mice when coadministered with a nonimmunogenic antigen, indicating stimulation of the adaptive as well as innate immune response.

Indexed as

Toll-Like Receptor 1Toll-Like Receptor 2Adaptive ImmunityAdjuvants, ImmunologicAnimalsCyclopropanesHumansMicePyrrolidinesAdjuvants, ImmunologicCyclopropanesdiprovocimPyrrolidinesTLR2 protein, humanTlr2 protein, mouseToll-Like Receptor 1Toll-Like Receptor 2

Identifiers

PMID35767437
PMCPMC9283309

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.