Evidence map›Paper›PMID 38543077›Full record

ArticlePharmaceuticals (Basel, Switzerland)2024

Targeting MutT Homolog 1 (MTH1) for Breast Cancer Suppression by Using a Novel MTH1 Inhibitor MA-24 with Tumor-Selective Toxicity.

Nannan Kang, Jun Ma, Yuling Hu, Rongrong Di, Lei Wang, Xuanling Zhang, Yisheng Lai, Yu Liu

Open access · goldAbstract read
In one paragraph

Article in Pharmaceuticals (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Review
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

8 authors at 1 institution in 1 country.

Nannan KangSchool of Life Science & Technology, China Pharmaceutical University, Nanjing 211198, China.ORCID 0000-0001-5746-5691
Jun MaCenter of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
Yuling HuSchool of Life Science & Technology, China Pharmaceutical University, Nanjing 211198, China.
Rongrong DiSchool of Life Science & Technology, China Pharmaceutical University, Nanjing 211198, China.
Lei WangCenter of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
Xuanling ZhangSchool of Life Science & Technology, China Pharmaceutical University, Nanjing 211198, China.
Yisheng LaiCenter of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
Yu LiuSchool of Life Science & Technology, China Pharmaceutical University, Nanjing 211198, China.
China Pharmaceutical University · CN

Funding

National Natural Science Foundation of China 22277142National Natural Science Foundation of China 82204452
6 · The paper itself

Abstract

backgroundBreast cancer is a commonly diagnosed cancer worldwide. Human MutT homolog 1 (MTH1) is found to be elevated in breast tumors and cancer cells need MTH1 for survival. Pharmacological inhibition of MTH1 may be potentially beneficial in the treatment of breast cancer.

methodsMA-24 was screened by malachite green colorimetric assay for MTH1 inhibitors and the kinetic characteristics of MA-24 were assessed. The features of MA-24's binding with MTH1 were ascertained through molecular docking, and the cytotoxic activity of MA-24 was validated in vitro and in vivo. Target engagement assays, comet assay, and Western blot confirmed the intracellular target and mechanism of MA-24.

resultsMA-24 shows potent antitumor bioactivity both in vitro and in vivo. MA-24 competitively inhibited the MTH1 and further induced DNA strand breaks, leading to increased apoptosis of cancer cells depending on the upregulation of the cleaved-caspase 3-cleaved-PARP axis. In particular, MA-24 exhibited a powerful efficacy and safety in vivo (tumor growth inhibition rate: 61.8%).

conclusionsMA-24 possesses a broad spectrum of breast cancer cytotoxicity and offered valuable insights for overcoming the challenges of chemotherapy-related toxicity, which holds great potential for the further development MA-24 as an anti-cancer drug.

Indexed as

antitumor activitybreast cancerMA−24MutT homolog 1(MTH1)oxidized nucleotide

Identifiers

PMID38543077
PMCPMC10974945
OpenAlexW4392096586

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.