Evidence map›Paper›PMID 37658623›Full record

ArticleCancer medicine2023

SIRT2 inhibitor SirReal2 enhances anti-tumor effects of PI3K/mTOR inhibitor VS-5584 on acute myeloid leukemia cells.

Yiming Luo, Haijun Zhao, Jingtao Zhu, Liyi Zhang, Jie Zha, Li Zhang, Yi Ding, Xinyi Jian, Junjie Xia, Bing Xu and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 24% of its field
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

8 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. The Yin-Yang balance of SIRT1 and SIRT2 in cancer metabolic remodeling.International journal of biological sciences · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. 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

11 authors at 4 institutions in 1 country.

Yiming LuoDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, Fujian, China.ORCID 0000-0002-1729-7002
Haijun ZhaoDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Jingtao ZhuDepartment of Gastrointestinal Oncology Surgery, Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
Liyi ZhangDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Jie ZhaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Li ZhangDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Yi DingDepartment of Pathology, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, China.
Xinyi JianGraduate College of Fujian Medical University, Fuzhou, Fujian, China.
Junjie XiaOrgan Transplantation Institute of Xiamen University, Xiamen, Fujian, China.
Bing XuDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Zhongquan QiOrgan Transplantation Institute of Xiamen University, Xiamen, Fujian, China.
Fujian Medical University · CNFirst Affiliated Hospital of Xiamen University · CNGuangxi University · CNXiamen University · CN

Funding

Xiamen Cell Therapy Research Center 3502220214001
6 · The paper itself

Abstract

backgroundAcute myeloid leukemia (AML) is a highly aggressive form of cancer that is frequently diagnosed in adults and small molecule inhibitors have gained significant attention as a potential treatment option for AML.

methodsThe up-regulated genes in AML were identified through bioinformatics analysis. Potential candidate agents were selected through pharmacogenomics analysis. Proteomic experiments were conducted to determine the molecular mechanism after inhibitor treatment. To evaluate drug synergy, both cellular functional experiments and an AML mouse model were used.

resultsThrough bioinformatics analysis, we conducted a screening for genes that are highly expressed in AML, which led to the identification of nine small-molecule inhibitors. Among these inhibitors, the PI3K/mTOR inhibitor VS-5584 demonstrated significant effectiveness in inhibiting AML cell proliferation at low concentrations. Further testing revealed that VS-5584 induced apoptosis and cycle arrest of AML cells in a dose- and time-dependent manner. Proteomics analysis showed significant changes in protein expression profiles of AML cells after VS-5584 treatment, with 287 proteins being down-regulated and 71 proteins being up-regulated. The proteins that exhibited differential expression were primarily involved in regulating the cell cycle and apoptosis, as determined by GO analysis. Additionally, KEGG analysis indicated that the administration of VS-5584 predominantly affected the P53 and SIRT2 signaling pathways. The use of SIRT2 inhibitor SirReal2 alongside VS-5584 caused a significant reduction in the half-maximal inhibitory concentration (IC

conclusionsTaken together, the PI3K/mTOR inhibitor VS-5584 was effective in suppressing AML cell proliferation. PI3K/mTOR inhibitor combined with SIRT2 inhibitor exhibited a synergistic inhibitory effect on AML cells. Our findings offer promising therapeutic strategies and drug candidates for the treatment of AML.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsLeukemia, Myeloid, AcuteMTOR InhibitorsPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsSirtuin 2TOR Serine-Threonine KinasesAnimalsApoptosisCell Line, TumorCell ProliferationDrug SynergismHumansMiceProteomicsSignal TransductionMTOR InhibitorsMTOR protein, humanPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsSirtuin 2TOR Serine-Threonine Kinasesacute myeloid leukemiaanti-tumor effectPI3K/mTORSIRT2

Identifiers

PMID37658623
PMCPMC10557894
OpenAlexW4386386664

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.