Protein kinase inhibitor effects on P-glycoprotein (P-gp) activity and expression in various cell lines
Why this work is in the frame
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Bibliographic record
Abstract
Little is known about potential influences of kinase pathway modulation on expression and activity of P-glycoprotein (P-gp). A protein kinase inhibitor (PKI) library was screened, to determine its effects on activity and expression of P-gp, in various cell lines. Cell lines were incubated with PKI for 24 h. Subsequent P-gp substrate accumulation studies were performed. Changes in P-gp activity and/or expression ≥ 25% compared to control were considered hits. Kinase pathways identified as P-gp activity hits were examined for their ability to modulate permeability. PKI families GSK-3, Craf1 and VEGFR2 and Tie-2, significantly modulated P-gp activity in the MDCK cell line. PKI families GSK-3, Iκκ and Jnk2/3 significantly modulated P-gp activity in the Caco-2 cell line. Few P-gp activity hits significantly modulated P-gp expression. PKIs modulate P-gp activity more than P-gp expression in a cell line dependent manner, excluding GSK-3 PKI family, which appears to be cell line independent.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it