Evidence map›Paper›PMID 42570378›Full record

ArticleBioorganic chemistry2026

Synthesis and evaluation of 3,5-disubstituted isothiazolo[4,5-b]pyridines, pyrazolo[4,3-b]pyridines and isothiazolo[3,4-b]pyrazines as inhibitors of PIKfyve.

Ling-Jie Gao, Mathy Froeyen, Chieh-Wen Lo, Do Hoang Nhu Tran, Tom Van Loy, Dominique Schols, Jef Rozenski, Wim Dehaen, Shirit Einav, Steven De Jonghe

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic 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

10 authors.

Ling-Jie GaoKU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Herestraat 49, Box 1030, 3000 Leuven, Belgium.
Mathy FroeyenKU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Herestraat 49, Box 1030, 3000 Leuven, Belgium.
Chieh-Wen LoDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Do Hoang Nhu TranDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Tom Van LoyKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Molecular, Structural and Translational Virology Research Group, Herestraat 49, Box 1043, 3000 Leuven, Belgium.
Dominique ScholsKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Molecular, Structural and Translational Virology Research Group, Herestraat 49, Box 1043, 3000 Leuven, Belgium.
Jef RozenskiKU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Herestraat 49, Box 1030, 3000 Leuven, Belgium.
Wim DehaenKU Leuven, Department of Chemistry, Sustainable Chemistry for Metals and Molecules, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
Shirit EinavDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Biohub, San Francisco, California, 94158, USA.
Steven De JongheKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Molecular, Structural and Translational Virology Research Group, Herestraat 49, Box 1043, 3000 Leuven, Belgium. Electronic address: steven.dejonghe@kuleuven.be.

Funding

Advancing the development of a novel class of small molecules for treating pan-coronavirus infectionsR01AI158569 · NIAID · STANFORD UNIVERSITY · PI EINAV, SHIRIT · 2021 to 2025
$3.7M
NIAID NIH HHS R01 AI158569
6 · The paper itself

Abstract

Various 3,5-disubstituted isothiazolo[4,3-b]pyridines were previously shown to be potent inhibitors of the lipid kinase PIKfyve, displaying broad-spectrum antiviral activity. To further study their structure-activity relationship and to discover novel skeletons as antivirally active PIKfyve inhibitors, a scaffold hopping strategy was applied yielding isothiazolo[4,5-b]pyridines, pyrazolo[4,3-b]pyridines and isothiazolo[3,4-b]pyrazines. Among the newly synthesized scaffolds, the isothiazolo[3,4-b]pyrazines were the most promising, displaying potent and selective PIKfyve inhibition in a biochemical assay, and, in addition, showing antiviral activity against SARS-CoV-2 (in the low μM range). Finally, molecular docking of the various scaffolds in the ATP-binding site of PIKfyve allowed to rationalize their differences in PIKfyve inhibitory activity.

Indexed as

Antiviral AgentsPhosphoinositide-3 Kinase InhibitorsPyrazinesPyridinesAnimalsCOVID-19 Drug TreatmentHumansMolecular Docking SimulationMolecular StructurePhosphatidylinositol 3-KinasesPyrazolesSARS-CoV-2Structure-Activity RelationshipAntiviral AgentsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPIKFYVE protein, humanPyrazinesPyrazolesPyridinesIsothiazolo[3,4-b]pyrazineIsothiazolo[4,5-b]pyridinePIKfyvePyrazolo[4,3-b]pyridineSARS-CoV-2

Identifiers

PMID42570378
PMCPMC13533896

What OpenQuestion holds

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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.