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Record W4392913891 · doi:10.32920/25417297

The Synthesis of Molecular Probes Based on Cystic Fibrosis Drugs for Biological Research

2024· preprint· en· W4392913891 on OpenAlexafffund
Philip Junor

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldChemistry
TopicClick Chemistry and Applications
Canadian institutionsToronto Metropolitan University
FundersSickkids Research InstituteHospital for Sick Children
KeywordsIvacaftorPotentiatorCystic fibrosisCystic fibrosis transmembrane conductance regulatorMutationPharmacologyDrugMedicineGeneChemistryComputational biologyBiologyGeneticsInternal medicine

Abstract

fetched live from OpenAlex

<p>Cystic fibrosis (CF) is a genetic disorder caused by a mutation in the gene that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. These mutations either impair trafficking to thecell membrane, reducefunction as ananion channel,orboth. Ivacaftor(a channel potentiator) was the first FDA-approved drug that treats the underlying cause of CF, specifically for patients with the G551D mutation. Shortly after, Orkambi, a combination of ivacaftor and the trafficking corrector lumacaftor was FDA-approved for patients homozygous for the F508del mutation. Based onclinical studies, itisreportedthatOrkambi has amodesteffect onlung function due to the negative impact of ivacaftor on the stability of F508del CFTR. Ivacaftor and lumacaftor were discovered and optimized through functional bioassays, and their interaction at the molecular level is not fully understood. To better understand the drug-protein interaction and inform the development of better CF drugs, molecular probes have been synthesized based on the structures of ivacaftor and lumacaftor.</p>

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)0.001
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 score0.289
Threshold uncertainty score0.516

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
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 science0.0010.001
Research integrity0.0000.001
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 head0.057
GPT teacher head0.357
Teacher spread0.299 · 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

Citations0
Published2024
Admission routes2
Has abstractyes

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