Evidence map›Paper›PMID 41795418›Full record

ArticleEuropean journal of medicinal chemistry2026

Identification and optimization of first-in-class RNA helicase inhibitors of DDX1, LGP2, and MDA5.

Xiaowen Wang, Feijun Wang, Deyu Kong, Dilipkumar Uredi, Fengling Li, Feng Li, Jayachandra Rayadurgam, Hanxuan Li, Esther Wolf, U Hang Chan and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

20 authors.

Xiaowen WangDepartment of Chemistry, University of Missouri, Columbia, MO, 65211, USA.
Feijun WangCenter for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Deyu KongCenter for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Dilipkumar UrediCenter for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Fengling LiStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Feng LiCenter for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Jayachandra RayadurgamCenter for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Hanxuan LiCenter for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Esther WolfStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada; Department of Chemistry, York University, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
U Hang ChanDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Irene ChauStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Hong ZengStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Julia Garcia PerezStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada.
Derek J WilsonDepartment of Chemistry, York University, Toronto, ON, Canada.
Frances M BashoreStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Xiaodong WangCenter for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Levon HalabelianStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Kevin J FrankowskiCenter for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Dmitri KireevDepartment of Chemistry, University of Missouri, Columbia, MO, 65211, USA. Electronic address: dmitri.kireev@missouri.edu.
Alison D AxtmanStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. Electronic address: alison.axtman@unc.edu.

Funding

TREAT AD Structural Biology CoreU54AG065187 · NIA · EMORY UNIVERSITY · PI ALLAN I LEVEY · 2019 to 2026
$69.7M
Request for a 500 MHz NMR console and nitrogen-cooled cryoprobeS10OD032476 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LEE, ANDREW L · 2022 to 2022
$599k
NIA NIH HHS U54 AG065187NIH HHS S10 OD032476
6 · The paper itself

Abstract

RNA helicases are essential, dynamic proteins that consume ATP to unwind and rearrange RNA. These activities place RNA helicases in roles as central mediators of signaling, especially those pathways dependent on RNA metabolism. Their binding of both ATP and RNA, as well as limited literature examples of small molecule ligands, support the tractability of RNA helicases. We employed structure-based virtual screening to rationally identify ligands that occupy the ATP-binding site of three human DExD/H-box RNA helicases: MDA5, LGP2, and DDX1. Following alignment of the well conserved nucleotide binding pocket for these RNA helicases, we docked and refined the list of potential ligands from the MolPort-2022-03 ligand library of ∼3.7 million members. A chemical lead with favorable solubility emerged from the 144 purchased compounds, which were evaluated in MDA5, LGP2, and DDX1 ATPase assays as well as corresponding SPR assays. It was found to be ATP un-competitive for MDA5 and to have similar affinity for the three RNA helicases. Analogs of the lead compound were designed to optimize the potency and selectivity of the scaffold, yielding both pan-helicase inhibitors and other analogs that are biased toward MDA5 inhibition.

Indexed as

DEAD-box RNA HelicasesEnzyme InhibitorsInterferon-Induced Helicase, IFIH1RNA HelicasesDose-Response Relationship, DrugHumansMolecular Docking SimulationMolecular StructureStructure-Activity RelationshipDDX1 protein, humanDEAD-box RNA HelicasesDHX36 protein, humanEnzyme InhibitorsInterferon-Induced Helicase, IFIH1RNA Helicases

Identifiers

PMID41795418
PMCPMC13051341

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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.