SP071APABETALONE (RVX-208), A SELECTIVE BROMODOMAIN AND EXTRA-TERMINAL (BET) PROTEIN INHIBITOR, DECREASES ABUNDANCE AND ACTIVITY OF COMPLEMENT PROTEINS IN VITRO, IN MICE AND IN CLINICAL STUDIES
Bibliographic record
Abstract
Introduction and Aims: RVX-208, an orally active small molecule, reduced incidence of major acute cardiac events in patients with cardiovascular disease (CVD) and potentially improved eGFR in a subpopulation with chronic kidney disease (CKD) in phase II clinical studies. RVX-208 inhibits the epigenetic readers bromodomain and extraterminal (BET) proteins by competing with acetylated lysines on histones tails that are associated with active transcription. Previously, microarray studies of primary human hepatocytes (PHH) have shown a downregulation of several complement genes (19 of 26). Since activation of complement in the kidney has been associated with renal disease and reduction in complement activation is beneficial for kidney function, we have examined the effect of RVX-208 on complement expression and activity in vitro, in mice and in clinical samples. Methods: Effects of RVX-208 on mRNA expression and secretion of complement proteins was examined in cultured PHH. Expression of complement genes was studied in mice treated with RVX-208 (150 mg/kg, 3 days, b.i.d.). Circulating complement proteins and complement activity were quantified in clinical samples using proteomics approaches and hemolytic assays, respectively.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".