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Record W4410251019 · doi:10.1038/s43856-025-00880-0

The non-cytotoxic small molecule NPB does not inhibit BAD phosphorylation and forms colloidal aggregates

2025· letter· en· W4410251019 on OpenAlexafffund
John Maringa Githaka, Tomás Gutiérrez, Zhuang Zhuang Han, Joseph O. Primeau, Heather Muranyi, Howard S. Young, Brian D. Sykes, Olivier Julien, Ing Swie Goping

Bibliographic record

VenueCommunications Medicine · 2025
Typeletter
Languageen
FieldBiochemistry, Genetics and Molecular Biology
Topic14-3-3 protein interactions
Canadian institutionsUniversity of Alberta
FundersCanadian Institutes of Health ResearchGovernment of Canada
KeywordsCytotoxic T cellColloidPhosphorylationChemistryMoleculeSmall moleculeBiophysicsCell biologyMaterials scienceBiochemistryBiologyOrganic chemistryIn vitro

Abstract

fetched live from OpenAlex

Therapies that induce apoptosis in cancer cells are critically important in clinical oncology. In a recent Communications Medicine article 1 and Proceedings of the National Academy of Sciences article 2 , a small molecule, NPB, was reported to induce cancer cell-specific cell death by inhibiting phosphorylation of the apoptotic protein, BAD. Using the same breast and ovarian cancer cell lines as the original reports, we endeavored to replicate these studies. We found that NPB did not inhibit BAD phosphorylation nor induce cell death. Furthermore, we observed that NPB forms large colloidal aggregates that are incompatible with the proposed mechanism of action, which posits that NPB binds to intracellular BAD. Thus, the prospect of NPB as a BAD-inhibitor that induces cancer cell apoptosis should be re-evaluated.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Commentary · Consensus signal: Commentary
Teacher disagreement score0.535
Threshold uncertainty score0.841

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.014
GPT teacher head0.275
Teacher spread0.261 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreCommentary

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
Published2025
Admission routes2
Has abstractyes

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