SP671CALCINEURIN INHIBITION WITHOUT THERAPEUTIC DRUG MONITORING?
Bibliographic record
Abstract
Introduction and Aims: The goal of treatment in lupus nephritis (LN) is to induce remission, preserve native renal function and minimize side effects. Voclosporin (VCS) is a novel calcineurin inhibitor intended for use in the treatment of autoimmune diseases and the prevention of organ graft rejection. Voclosporin was created by adding a single carbon extension to the amino acid-1 (AA1) region of cyclosporine A (CsA). X-Ray crystallography studies have shown that this addition alters cyclophilin-voclosporin complex binding to the catalytic and regulatory subunits in calcineurin. This change in binding has increased the potency of voclosporin relative to CsA and shifted the primary site for voclosporin metabolism to the amino acid-9 position. This leads to lower overall metabolite loads than seen for CsA resulting in less competitive antagonism with voclosporin. The combination of increased potency and a change in metabolite profile for voclosporin allows for administration of lower doses, less pharmacokinetic-pharmacodynamic variability and a potentially improved safety profile compared with other calcineurin inhibitors. Previously published data have demonstrated the strong correlation between VCS concentrations and efficacy which might allow for accurate dosing of patients.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".