Dual-acting 5-Fluorodeoxyuridine (FUdR) Prodrugs: Cell Death Induced by 3’-O-retinoyl-5-fluoro-2’-deoxyuridine and 5’-O-[bis(2,2,2,-trichloroethyl) phosphoryl-3’-O-butanoyl]-5-fluoro-2’-deoxyuridine
Bibliographic record
Abstract
Several novel 5-fluoro-2'-deoxyuridine (FUdR) prodrugs with postulated dual mechanisms of anticancer activity based on nucleoside cytotoxicity and cell differentiation induced by retinoic acid/butyric acid have been reported. The O-retinoyl-and O-butanoyl-esters of FUdR were reported to be more potent and had broader anticancer spectra than either FUdR or 5-fluorouracil (FU) against a bank of human cancer cell lines. The induction of necrosis or apoptosis in HL-60 cells by 3'-O-retinoyl-5-fluoro-2'-deoxyuridine (RFUdR) and the masked butyryl ester nucleotide, 5'-O-bis(trichloroethyl)phosphoryl-3'-O-butanoyl-5-fluoro-2'-deoxyuridine (BTCEP-BFUdR), is now reported. Apoptosis was the major pathway of HL-60 cell death caused by RFUdR (1 10 -5 M), independent of the exposure time. In contrast, apoptosis and necrosis were equally evident after exposure to BTCEP-BFUdR (1 10 -5 M) for 48 h, which is similar to the effect of FUdR. These in vitro data support a cytotoxicity model in which release of the nucleoside (FUdR) and the cell differentiator (all-trans retinoic acid, RA or butyrate, NaBu) from the respective prodrugs act synergistically to induce greater cell killing.
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How this classification was reachedexpand
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".