Evidence map›Paper›PMID 33037737›Full record

ArticleCancer science2020

Efficacy of the novel tubulin polymerization inhibitor PTC-028 for myelodysplastic syndrome.

Cheng Zhong, Kensuke Kayamori, Shuhei Koide, Daisuke Shinoda, Motohiko Oshima, Yaeko Nakajima-Takagi, Yurie Nagai, Naoya Mimura, Emiko Sakaida, Satoshi Yamazaki and 10 more

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2020. 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 23% 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, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activity.Journal of enzyme inhibition and medicinal chemistry · 2023
    Article
  5. Review
  6. Article
  7. How to Select Firefly Luciferin Analogues for In Vivo Imaging.International journal of molecular sciences · 2021
    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

20 authors at 8 institutions in 2 countries.

Cheng ZhongDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Kensuke KayamoriDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Shuhei KoideDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Daisuke ShinodaDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Motohiko OshimaDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yaeko Nakajima-TakagiDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yurie NagaiDepartment of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan.
Naoya MimuraDepartment of Transfusion Medicine and Cell Therapy, Chiba University Hospital, Chiba, Japan.
Emiko SakaidaDepartment of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan.
Satoshi YamazakiLaboratory of Stem Cell Therapy, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Satoshi IwanoLaboratory for Cell Function Dynamics, Center for Brain Science, RIKEN, Saitama, Japan.
Atsushi MiyawakiLaboratory for Cell Function Dynamics, Center for Brain Science, RIKEN, Saitama, Japan.
Ryoji ItoHumanized Model Laboratory, Central Institute for Experimental Animals, Kanagawa, Japan.
Kaoru TohyamaDepartment of Laboratory Medicine, Kawasaki Medical School, Okayama, Japan.ORCID https://orcid.org/0000-0002-0812-9816
Kiyoshi YamaguchiDivision of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0003-2113-4369
Yoichi FurukawaDivision of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
William LennoxPTC Therapeutics, South Plainfield, NJ, USA.
Josephine SheedyPTC Therapeutics, South Plainfield, NJ, USA.
Marla WeetallPTC Therapeutics, South Plainfield, NJ, USA.
Atsushi IwamaDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0001-9410-8992
The University of Tokyo · JPChiba University · JPPTC Therapeutics (United States) · USRIKEN Center for Brain Science · JPCentral Institute for Experimental Animals · JPChiba University Hospital · JPKawasaki Medical School · JPUniversity of Tsukuba · JP

Funding

Ministry of Education, Culture, Sports, Science and Technology 19H05653Ministry of Education, Culture, Sports, Science and Technology 19H05746
6 · The paper itself

Abstract

Monomer tubulin polymerize into microtubules, which are highly dynamic and play a critical role in mitosis. Therefore, microtubule dynamics are an important target for anticancer drugs. The inhibition of tubulin polymerization or depolymerization was previously targeted and exhibited efficacy against solid tumors. The novel small molecule PTC596 directly binds tubulin, inhibits microtubule polymerization, downregulates MCL-1, and induces p53-independent apoptosis in acute myeloid leukemia cells. We herein investigated the efficacy of PTC-028, a structural analog of PTC596, for myelodysplastic syndrome (MDS). PTC-028 suppressed growth and induced apoptosis in MDS cell lines. The efficacy of PTC028 in primary MDS samples was confirmed using cell proliferation assays. PTC-028 synergized with hypomethylating agents, such as decitabine and azacitidine, to inhibit growth and induce apoptosis in MDS cells. Mechanistically, a treatment with PTC-028 induced G2/M arrest followed by apoptotic cell death. We also assessed the efficacy of PTC-028 in a xenograft mouse model of MDS using the MDS cell line, MDS-L, and the AkaBLI bioluminescence imaging system, which is composed of AkaLumine-HCl and Akaluc. PTC-028 prolonged the survival of mice in xenograft models. The present results suggest a chemotherapeutic strategy for MDS through the disruption of microtubule dynamics in combination with DNA hypomethylating agents.

Indexed as

AnimalsAntimetabolites, AntineoplasticApoptosisBenzimidazolesCell Line, TumorCell ProliferationDecitabineG2 PhaseHeterograftsHL-60 CellsHumansMiceMyelodysplastic SyndromesPaclitaxelPyrazinesSequence Analysis, RNAAntimetabolites, AntineoplasticBenzimidazolesDecitabinePaclitaxelPTC-028PTC596PyrazinesTubulinTubulin ModulatorsVincristinechemotherapyDNA hypomethylating agentsMyelodysplastic syndromeTubulin polymerization inhibitor

Identifiers

PMID33037737
PMCPMC7734154
OpenAlexW3092104439

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.