Evidence map›Paper›PMID 38085423›Full record

ArticleInvestigational new drugs2024

Synergistic effect of adavosertib and fimepinostat on acute myeloid leukemia cells by enhancing the induction of DNA damage.

Yue Wang, Xingyu Lin, Yue Wang, Guan Wang

Abstract read
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In one paragraph

Article in Investigational new drugs, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Yue Wang *National Engineering Laboratory for AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun City, Jilin Province, China.
Xingyu Lin *Department of Thoracic Surgery, the First Hospital of Jilin University, Changchun, China.
Yue WangDepartment of Pediatric Hematology, the First Hospital of Jilin University, 1 Xinmin Street, Changchun City, Jilin Province, China. wang_yue@jlu.edu.cn.
Guan WangNational Engineering Laboratory for AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun City, Jilin Province, China. wg10@jlu.edu.cn.

Funding

National Natural Science Foundation of China NSFC82100076Projects of Jilin Province Science and Technology Development Plan 20220101284JC
6 · The paper itself

Abstract

In recent years, a number of novel pharmaceutical agents have received approval for the management of acute myeloid leukemia (AML). However, there is still ample opportunity for enhancing efficacy. The Wee1 inhibitor adavosertib (ADA) shows promise for the treatment of AML. Based on the effect of drugs on DNA damage, we conducted a combination study involving ADA and fimepinostat (CUDC-907), a dual inhibitor of PI3K and histone deacetylase (HDAC). We observed that the combination of CUDC-907 and ADA exhibited a synergistic effect in enhancing the antileukemic activity in both AML cell lines and primary patient samples, demonstrating through flow cytometry analysis and MTT assay, respectively. Additionally, our study revealed that CUDC-907 has the ability to augment ADA-induced DNA damage, as determined by the measurement of γH2AX levels and the implementation of the alkaline comet assay. Through the utilization of western blotting analyses, targeted inhibitors, and ectopic overexpression, we propose that the downregulation of Wee1, CHK1, RNR, and c-Myc are the potential mechanisms. Our data support the development of ADA in combination with CUDC-907 for the treatment of AML.

Indexed as

Leukemia, Myeloid, AcuteMorpholinesPyrazolesPyrimidinesPyrimidinonesSulfur CompoundsDNA DamageHumansadavosertibfimepinostatMorpholinesPyrazolesPyrimidinesPyrimidinonesSulfur CompoundsAcute myeloid leukemiaAdavosertibCombination therapyDNA damage responseFimepinostat

Identifiers

PMID38085423

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.