Evidence map›Paper›PMID 41038162›Full record

ArticleCell chemical biology2025

RAGE-mediated activation of the formin DIAPH1 and human macrophage inflammation are inhibited by a small molecule antagonist.

Gregory G Theophall, Michaele B Manigrasso, Parastou Nazarian, Aaron Premo, Sergey Reverdatto, Gautham Yepuri, David S Burz, Sally M Vanegas, Kaamashri Mangar, Yanan Zhao and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Review
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  5. Review
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Gregory G TheophallDepartment of Chemistry, State University of New York at Albany, Albany, NY 12222, USA.
Michaele B ManigrassoDiabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA.
Parastou NazarianDepartment of Chemistry, State University of New York at Albany, Albany, NY 12222, USA.
Aaron PremoDepartment of Chemistry, State University of New York at Albany, Albany, NY 12222, USA.
Sergey ReverdattoDepartment of Chemistry, State University of New York at Albany, Albany, NY 12222, USA.
Gautham YepuriDiabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA.
David S BurzDepartment of Chemistry, State University of New York at Albany, Albany, NY 12222, USA.
Sally M VanegasDepartment of Medicine, New York Grossman School of Medicine, New York, NY 10016, USA.
Kaamashri MangarDiabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA.
Yanan ZhaoDivision of Biostatistics, Department of Population Health, New York University School of Medicine, New York, NY 10016, USA.
Huilin LiDivision of Biostatistics, Department of Population Health, New York University School of Medicine, New York, NY 10016, USA.
Robert J DeVitaRJD Medicinal Chemistry and Drug Discovery Consulting LLC, Westfield, NJ 07091, USA.
Ravichandran RamasamyDiabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA.
Ann Marie SchmidtDiabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA. Electronic address: annmarie.schmidt@nyulangone.org.
Alexander ShekhtmanDepartment of Chemistry, State University of New York at Albany, Albany, NY 12222, USA. Electronic address: ashekhtman@albany.edu.

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1M
Project 3: RAGE/DIAPH1 interactions and cellular stressP01HL146367 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SCHMIDT, ANN MARIE · 2019 to 2023
$12.5M
Targeting RAGE-mDia1 in Diabetic Complications: Mechanisms and TherapeuticsR24DK103032 · NIDDK · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI RAMASAMY, RAVICHANDRAN, SCHMIDT, ANN MARIE · 2014 to 2018
$4.2M
Targeting RAGE/DIAPH1: Novel Therapeutic Strategy for Diabetic ComplicationsR01DK122456 · NIDDK · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI RAMASAMY, RAVICHANDRAN, SCHMIDT, ANN MARIE · 2020 to 2024
$3.1M
Real Time (RT) In-cell NMR technology to study protein interactions in live cellsR01GM085006 · NIGMS · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI SHEKHTMAN, ALEXANDER · 2010 to 2021
$2.4M
NCI NIH HHS P30 CA016087NHLBI NIH HHS P01 HL146367NIDDK NIH HHS R01 DK122456NIDDK NIH HHS R24 DK103032NIGMS NIH HHS R01 GM085006
6 · The paper itself

Abstract

RAGE and its intracellular effector molecule, the actin polymerase DIAPH1, mediate inflammation and the complications of diabetes. Using NMR spectroscopy and mass spectrometry, we built a structural model of the RAGE-DIAPH1 complex, revealing how binding of the cytoplasmic tail of RAGE (ctRAGE) to DIAPH1 stimulates its actin polymerization activity, which is inhibited by a small molecule antagonist of RAGE-DIAPH1 interaction, RAGE406R. The solution structure of the RAGE406R - ctRAGE suggests that RAGE406R prevents the formation of the RAGE-DIAPH1. FRET, actin polymerization assays, smooth muscle cell migration, and THP1 cell inflammation experiments, together with the in vivo interrogation of the effects of RAGE406R in mouse models of inflammation and diabetic wound healing, support this mode of RAGE-DIAPH1 antagonism. Finally, the treatment of macrophages differentiated from peripheral blood-derived mononuclear cells from humans with type 1 diabetes with RAGE406R reduces the mRNA expression of the chemokine CCL2, diminishing the expression of a key node in the inflammatory response.

Indexed as

ForminsInflammationMacrophagesReceptor for Advanced Glycation End ProductsSmall Molecule LibrariesAnimalsHumansMiceDIAPH1 protein, humanForminsReceptor for Advanced Glycation End ProductsSmall Molecule Librariesactin polymerizationcross-linkingdiabetesDIAPH1intrinsically disordered regionsmass spectrometrymDia1NMRprotein-protein interactionsreceptor for advanced glycation end products

Identifiers

PMID41038162
PMCPMC12614354

What OpenQuestion holds

Textmetadata
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.