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SGC-AAK1-1: A Chemical Probe Targeting AAK1 and BMP2K

2019· article· en· W2981620099 on OpenAlexfundno aff
Carrow I. Wells, Rafael M. Couñago, Juanita C. Limas, Tuanny L. Almeida, Jeanette Gowen Cook, David H. Drewry, Jonathan M. Elkins, O. Gileadi, Nirav Kapadia, Álvaro Lorente‐Macías, Julie E. Pickett, Alexander J. Riemen, Roberta R. Ruela-de-Sousa, Timothy M. Willson, Cunyu Zhang, William J. Zuercher, Reena Zutshi, Alison D. Axtman

Bibliographic record

VenueACS Medicinal Chemistry Letters · 2019
Typearticle
Languageen
FieldMedicine
TopicPeptidase Inhibition and Analysis
Canadian institutionsnot available
FundersStructural Genomics ConsortiumEshelman Institute for Innovation, University of North Carolina at Chapel HillNational Institute of General Medical SciencesMerck Sharp and DohmeInnovative Medicines InitiativeConselho Nacional de Desenvolvimento Científico e TecnológicoAbbVieNovartis PharmaCanada Foundation for InnovationMinisterio de Educación, Cultura y DeporteOntario Ministry of Economic Development and InnovationFundação de Amparo à Pesquisa do Estado de São PauloGenome CanadaBayerNational Cancer InstituteTakeda Pharmaceutical CompanyJanssen PharmaceuticalsMerck KGaAWellcome TrustNorth Carolina Biotechnology CenterHoward Hughes Medical InstitutePfizerBoehringer IngelheimNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsKinomeSmall moleculeChemistryCombinatorial chemistryChemical libraryYield (engineering)Computational biologyChemical biologyBiochemistryBiologyKinaseMaterials science

Abstract

fetched live from OpenAlex

Inhibitors based on a 3-acylaminoindazole scaffold were synthesized to yield potent dual AAK1/BMP2K inhibitors. Optimization furnished a small molecule chemical probe (SGC-AAK1-1, 25) that is potent and selective for AAK1/BMP2K over other NAK family members, demonstrates narrow activity in a kinome-wide screen, and is functionally active in cells. This inhibitor represents one of the best available small molecule tools to study the functions of AAK1 and BMP2K.

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 categoriesInsufficient payload (model declined to judge)
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 score0.010
Threshold uncertainty score1.000

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)0.0010.000

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 head0.005
GPT teacher head0.223
Teacher spread0.218 · 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.

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

Citations52
Published2019
Admission routes1
Has abstractyes

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