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Record W4223528634 · doi:10.1002/cmdc.202200161

Identification of 4‐Anilinoquin(az)oline as a Cell‐Active Protein Kinase Novel 3 (PKN3) Inhibitor Chemotype**

2022· article· en· W4223528634 on OpenAlexfundno aff
Christopher R. M. Asquith, Louisa Temme, Michael P. East, Tuomo Laitinen, Julie E. Pickett, Frank E. Kwarcinski, Parvathi Sinha, Carrow I. Wells, Gary L. Johnson, Reena Zutshi, David H. Drewry

Bibliographic record

VenueChemMedChem · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Kinase Regulation and GTPase Signaling
Canadian institutionsnot available
FundersNational Center for Advancing Translational SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesUniversity of North Carolina at Chapel HillNational Institutes of HealthCanada Foundation for InnovationInnovative Medicines InitiativeWellcome Trust
KeywordsChemotypeKinaseChemistryProtein kinase inhibitorIdentification (biology)Protein kinase ABiochemistryCancer researchBiologyComputational biology

Abstract

Abstract Deep annotation of a library of 4‐anilinoquin(az)olines led to the identification of 7‐iodo‐ N ‐(3,4,5‐trimethoxyphenyl)quinolin‐4‐amine 16 as a potent inhibitor (IC 50 =14 nM) of Protein Kinase Novel 3 (PKN3) with micromolar activity in cells. Compound 16 is a potential tool compound to study the cell biology of PKN3 and its role in pancreatic and prostate cancer and T‐cell acute lymphoblastic leukemia. These 4‐anilinoquin(az)olines may also be useful tools to uncover the therapeutic potential of PKN3 inhibition in a broad range of diseases.

Stored with the screening record, where it is evidence for the labels above.

How this classification was reachedexpand

The three-model screen

all 5,600 screened works →

All three models called this out of scope.

stratum: fund_new · design weight: 1678.90 (the sample is stratified; any rate computed without the weight is wrong)
Claude Opus 4.8OUT
genre: empirical
about Canada: no
confidence: high

Medicinal chemistry identification of a PKN3 kinase inhibitor chemotype.

GPT-5.6 (high)OUT
genre: empirical
about Canada: no
confidence: high

The work identifies a protein kinase inhibitor for cancer research, not a study of research.

Grok 4.5OUT
genre: empirical
about Canada: no
confidence: high

Medicinal chemistry identification of a PKN3 inhibitor chemotype; domain drug discovery.

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.000

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.234
Teacher spread0.225 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2022
Admission routes1
Has abstractyes

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