Abstract 1757: Elesclomol (STA-4783) is a potent inhibitor of topoisomerase II
Bibliographic record
Abstract
Abstract Elesclomol (STA-4783; N’1, N’3-dimethyl-N’1, N’3- bis(phenylcarbonothioyl)propanedihydrazide) is an anticancer drug that has received both fast track and orphan drug status from the FDA and is currently undergoing clinical trials. Elesclomol forms a strong 1:1 complex with copper(II) and may exert its anticancer activity through the induction of oxidative stress. In the studies reported here elesclomol was assessed for its ability to inhibit: 1) the growth of the human erythroleukemic K562 cell line and an etoposide-resistant K/VP.5 cell line; 2) the decatenation activity of DNA topoisomerase IIα; and 3) the relaxation activity of DNA topoisomerase I. Elesclomol was also evaluated for its ability to induce topoisomerase IIα-mediated double strand cleavage of pBR322 DNA and to form topoisomerase IIα-DNA covalent adducts in the cell-based ICE assay. Elesclomol inhibited K562 cell growth in the submicromolar concentration range. However, K/VP.5 cells were not cross-resistant. Elesclomol also strongly inhibited the decatenation activity of topoisomerase IIα in the low micromolar concentration range. Elesclomol may also act as topoisomerase IIα poison because it induced formation of linear DNA, though not as strongly as etoposide. In conclusion, these results show that elesclomol may, in part, inhibit cell growth through the targeting of topoisomerase II. Support: CIHR, a Canada Research Chair in Drug Development to B.B.H., a National Institutes of Health grant CA090787 to J.C.Y. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1757. doi:1538-7445.AM2012-1757
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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) | 0.001 | 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) | 0.007 | 0.003 |
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".