The Synthesis of Molecular Probes Based on Cystic Fibrosis Drugs for Biological Research
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.003 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".