Enhanced Lactone Stability of CZ48 in Blood Correlates to its Lack of Toxicity in Mice
Bibliographic record
Abstract
PURPOSE: The aim of this study was to correlate the relationship between the pharmacokinetic behaviors and the toxicity of a new investigational anticancer agent CZ48, a C20-propionate ester of camptothecin (CPT) in mice. METHODS: In this study, the safety and pharmacokinetics of oral doses of CZ48 were compared with the oral doses of CPT. Mice were administered orally one of three single doses of CZ48 (50, 200 and 1000 mg/kg) and two single doses of CPT (1.5 mg/kg and 6.0 mg/kg). Blood samples were collected from all mice at the defined time points after drug administration for assessment of plasma CZ48 and CPT concentrations. RESULTS: The study showed that CZ48 was very stable in mouse blood and the majority of this agent stayed intact as the lactone form when in circulation, with only a small fraction of the CZ48 molecules metabolized into CPT. The concentration of the metabolite CPT measured in the mouse blood was only 3% of the concentration found for the maximum tolerated dose (6.0 mg/kg) of plain CPT. The stability difference between CZ48 and CPT in blood was structurally explained by the geometry of these two molecules. CONCLUSION: The lack of toxicity of CZ48 at effective doses in mice is attributed to its enhanced stability in their blood.
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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) | 0.001 | 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 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".