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Record W3162753890 · doi:10.1002/cmdc.202100271

Front Cover: Getting a Grip on the Undrugged: Targeting β‐Catenin with Fragment‐Based Methods (9/2021)

2021· paratext· en· W3162753890 on OpenAlexaff
Dirk Kessler, Moriz Mayer, Stephan K. Zahn, Markus Zeeb, Simon Wöhrle, Andreas Bergner, Jens Bruchhaus, Tuncay Ciftci, Georg Dahmann, Maike Dettling, Sandra Döbel, Julian E. Fuchs, Leonhard Geist, Wolfgang Hela, Christiane Kofink, Roland Kousek, Franziska Moser, Teresa Puchner, Klaus Rumpel, Maximilian Scharnweber, Patrick Werni, B. Wolkerstorfer, Dennis Breitsprecher, Philipp Baaske, Mark Pearson, Darryl B. McConnell, Jark Böttcher

Bibliographic record

VenueChemMedChem · 2021
Typeparatext
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Degradation and Inhibitors
Canadian institutionsMicrosemi (Canada)
Fundersnot available
KeywordsFront coverProtein Data Bank (RCSB PDB)Fragment (logic)Transcription factorCateninCover (algebra)Transcription (linguistics)ChemistryComputational biologyBiologyStereochemistryComputer scienceBiochemistryAlgorithmSignal transductionPhilosophyGeneEngineering

Abstract

fetched live from OpenAlex

The Front Cover shows the discovered fragment in the process of binding to β-catenin bound to the transcription factor TCF4 and co-activator BCL9 (PDB ID: 2GL7). The electron density surrounding the ligand and the chemical shift perturbations observed in the fragment binding site represent the strong biophysical validation. The outreaching arm represents the prospective utility of this discovery to be used as a handle for proteolysis targeting chimeras (PROTACs) upon further optimization. More information can be found in the Communication by Dirk Kessler, Jark Böttcher et al. Cover art created by Mila Böttcher, Jark Böttcher, and Darryl B. McConnell.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Other · Consensus signal: Other
Teacher disagreement score0.205
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.001

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 head0.016
GPT teacher head0.283
Teacher spread0.267 · 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; both teacher heads agree on what is shown here.

Study designNot applicable
Domainnot available
GenreOther

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

Citations0
Published2021
Admission routes1
Has abstractyes

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