NSC101612 potently inhibits tumor cell growth and is a topoisomerase IIα catalytic inhibitor.
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 47, 2006 5533 The fully substituted quinone NSC101612 (5,6-bis((2-hydroxyethyl)thio)-1H-benzimidazole-4,7-dione) was examined for its ability to inhibit cell growth and to inhibit human DNA topoisomerase IIα (topo II). NSC101612 significantly inhibited the catalytic activity of topo II with an IC50 value of 0.33 μM. NSC101612 also inhibited the growth of human erythroleukemic K562 and Chinese hamster ovary (CHO) cells with IC50 values of 28 μM and 48 μM, respectively. NSC101612 was also examined for its ability to stabilize a DNA-topo II covalent complex and act as a topo II poison by measuring its ability to cleave pBR322 DNA to produce linear DNA. It did not induce pBR322 DNA cleavage suggesting that it is not a topo II poison. The growth inhibitory effects of NSC101612 on K562 and K/VP.5 cells (an etoposide-resistant cell line containing one-fifth the topo II content of the parental K562 cells) were not significantly different. These results also suggest that NSC101612 did not act as a topo II poison. NSC101612 did not detectably increase levels of γH2AX protein in K562 cells, indicating that this compound did not act by damaging DNA, further confirming that this compound did not act as a topo II poison. Our spectrophotometric results showed that the quinone compound NSC101612 quickly reacted with the sulfhydryl compounds dithiothreitol (DTT), glutathione (GSH) and cysteine. DTT partially protected topo II from inhibition by NSC101612. These results suggest that this compound may inhibit topo II by reacting with critical thiol groups on topo II. The fact that DTT did not completely protect topo II from NSC101612 suggests that reaction with sulfhydryl groups on topo II may not be the only mechanism by which NSC101612 acts. In conclusion, our results suggest that NSC101612 may inhibit cell growth in part by inhibiting the catalytic activity of topo II. Support: CIHR and a Canada Research Chair in Drug Development.
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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".