Evidence map›Paper›PMID 40803164›Full record

ArticleEuropean journal of medicinal chemistry2025

Discovery of antivirally active inhibitors of adaptor protein-2 associated kinase 1 based on various bicyclic heteroaromatic scaffolds derived from a 7-azaindole analogue.

Stijn Anthonissen, Wout Van Eynde, Marwah Karim, Ling-Jie Gao, Do Hoang Nhu Tran, Dominique Schols, Arnout Voet, Shirit Einav, Wim Dehaen, Steven De Jonghe

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 7-azaindole as privileged scaffold: Advances in drug design and structural modification.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
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

10 authors.

Stijn AnthonissenKU Leuven, Sustainable Chemistry for Metals and Molecules, Department of Chemistry, Celestijnenlaan 200F, B-3001, Leuven, Belgium.
Wout Van EyndeKU Leuven, Department of Chemistry, Biochemistry, Molecular and Structural Biology, Laboratory of Biomolecular Modelling and Design, Celestijnenlaan 200G, Box 2403, B-3001, Leuven, Belgium.
Marwah KarimDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, 94305, USA.
Ling-Jie GaoKU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Herestraat 49, B-3000, Leuven, Belgium.
Do Hoang Nhu TranDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, 94305, USA.
Dominique ScholsKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Molecular, Structural and Translational Virology Research Group, B-3000, Leuven, Belgium.
Arnout VoetKU Leuven, Department of Chemistry, Biochemistry, Molecular and Structural Biology, Laboratory of Biomolecular Modelling and Design, Celestijnenlaan 200G, Box 2403, B-3001, Leuven, Belgium.
Shirit EinavDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
Wim DehaenKU Leuven, Sustainable Chemistry for Metals and Molecules, Department of Chemistry, Celestijnenlaan 200F, B-3001, Leuven, Belgium.
Steven De JongheKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Molecular, Structural and Translational Virology Research Group, B-3000, Leuven, Belgium. Electronic address: steven.dejonghe@kuleuven.be.

Funding

EMERGING INFECTIOUS DISEASEST32AI007502 · NIAID · STANFORD UNIVERSITY · PI Prasanna Jagannathan, DAVID A. RELMAN · 1995 to 2026
$6.8M
NIAID NIH HHS T32 AI007502
6 · The paper itself

Abstract

Adaptor protein-2 associated kinase 1 (AAK1) has been proposed as a promising host target for the development of broad-spectrum antiviral agents. Different regioisomers, as well as scaffolds that were not explored before for their AAK1 affinity, were prepared that were derived from a known and potent 7-azaindole-based AAK1 inhibitor. This effort led to the discovery of various pyrrolo[2,3-b]pyridines, pyrazolo[3,4-b]pyridines and pyrazolo[3,4-d]pyrimidines with low nanomolar AAK1 binding affinity. The AAK1 data were rationalized by molecular modeling. Selected congeners displayed antiviral activity against dengue virus and Venezuelan equine encephalitis virus.

Indexed as

Antiviral AgentsDrug DiscoveryIndolesProtein Kinase InhibitorsDengue VirusDose-Response Relationship, DrugHumansMicrobial Sensitivity TestsModels, MolecularMolecular StructurePyridinesStructure-Activity Relationship7-azaindole dimerAntiviral AgentsIndolesProtein Kinase InhibitorsPyridinesAdaptor protein-2 associated kinase 1AntiviralsAzaindolePyrrolo[2,3-b]pyridine

Identifiers

PMID40803164
PMCPMC12756906

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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.