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Record W4296323280 · doi:10.1021/acs.jmedchem.2c00509

Discovery and Structural Characterization of Small Molecule Binders of the Human CTLH E3 Ligase Subunit GID4

2022· article· en· W4296323280 on OpenAlexafffund
Chetan K. Chana, Pierre Maisonneuve, Ganna Posternak, Nicolas G.A. Grinberg, Juline Poirson, Samara Mishelle Ona, Derek F. Ceccarelli, P. Mäder, Daniel J. St‐Cyr, Victor P.T. Pau, Igor Kurinov, Xiaojing Tang, Dongjing Deng, Weiren Cui, Wenji Su, Letian Kuai, Richard Söll, Mike Tyers, Hannes Röst, Robert A. Batey, Mikko Taipale, Anne‐Claude Gingras, Frank Sicheri

Bibliographic record

VenueJournal of Medicinal Chemistry · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Degradation and Inhibitors
Canadian institutionsInstitute for Research in Immunology and CancerUniversité de MontréalLunenfeld-Tanenbaum Research InstituteUniversity of Toronto
FundersNational Institute of General Medical SciencesCanadian Institutes of Health ResearchNational Institutes of Health
KeywordsChemistryUbiquitin ligaseProtein subunitSmall moleculeDNA ligaseStereochemistryIn vitroUbiquitinMoleculeEffectorUbiquitin-Protein LigasesBiochemistryBiophysicsDNAGeneBiology

Abstract

fetched live from OpenAlex

of 558 nM in cells with strong selectivity for GID4. X-ray co-structure determination revealed the basis for GID4-small molecule interactions. These results position GID4-CTLH as an E3 for TPD and provide candidate scaffolds for high-affinity moieties that bind GID4.

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)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.004
Threshold uncertainty score0.244

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.008
GPT teacher head0.221
Teacher spread0.214 · 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 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

Citations54
Published2022
Admission routes2
Has abstractyes

Explore more

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