Evidence map›Paper›PMID 41849779›Full record

ArticleJournal of medicinal chemistry2026

Identification and Validation of an Inhibitor of the Protein Kinases PIM and DYRK.

Gyula Bencze, Prabhadevi Venkataramani, Elad Elkayam, Keith D Rivera, Ankur Garg, Istvan Szabadakai, Laszlo Orfi, Leemor Joshua-Tor, Darryl J Pappin, Nicholas K Tonks

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2026. 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. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Gyula BenczeCold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York 11724, United States.
Prabhadevi VenkataramaniCold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York 11724, United States.ORCID 0000-0001-9106-0102
Elad ElkayamCold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York 11724, United States.
Keith D RiveraCold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York 11724, United States.
Ankur GargCold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York 11724, United States.
Istvan SzabadakaiVichem Chemie Ltd, Berlini u. 47-49-5.a épület III. emelet, Budapest 1045, Hungary.
Laszlo OrfiVichem Chemie Ltd, Berlini u. 47-49-5.a épület III. emelet, Budapest 1045, Hungary.
Leemor Joshua-TorCold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York 11724, United States.
Darryl J PappinCold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York 11724, United States.ORCID 0000-0002-8981-8401
Nicholas K TonksCold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York 11724, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fermented wheat germ extract (FWGE), a nutraceutical with reported anticancer properties, contains numerous biologically active molecules, but its therapeutic constituents remain unclear. In this study, we identify and characterize a novel small-molecule protein kinase inhibitor isolated from FWGE, designated F10V6W0. Through preparative high-performance liquid chromatography and structural elucidation via X-ray crystallography, this compound was revealed to be a unique benzothiazole. Kinase profiling demonstrated its selectivity toward PIM and DYRK protein kinase families. A chemically synthesized version (CSH-4044), mirrored the activity of the natural product, confirming structural integrity and biological equivalence. We determined the cocrystal structure of CSH-4044 bound to PIM1, revealing ATP-competitive binding and critical hydrophobic and hydrogen-bonding interactions. Functionally, CSH-4044 suppressed PIM3-driven BAD phosphorylation in pancreatic cancer cells and reduced DYRK1A-mediated Tau phosphorylation in neuronal cells. Our findings position CSH-4044 as a promising lead for targeting PIM and DYRK kinase families and highlight FWGE as a potential therapeutic compounds.

Indexed as

BenzothiazolesProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins c-pim-1Cell Line, TumorCrystallography, X-RayDyrk KinasesHumansModels, MolecularPhosphorylationProtein-Tyrosine KinasesStructure-Activity RelationshipBenzothiazolesDyrk KinasesProtein Kinase InhibitorsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-pim-1proto-oncogene proteins pim

Identifiers

PMID41849779
PMCPMC13071872

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.