Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin

Ting Chun Kuo, Ling Wei Li, Szu Hua Pan, Jim Min Fang, Jyung Hurng Liu, Ting Jen Cheng, Chia Jen Wang, Pei Fang Hung, Hsuan Yu Chen, Tse-Ming Hong, Yuan Ling Hsu, Chi Huey Wong, Pan Chyr Yang

研究成果: Article

9 引文 (Scopus)

摘要

Microtubule targeting agents (MTAs) constitute a class of drugs for cancer treatment. Despite many MTAs have been proven to significantly improve the treatment outcomes of various malignancies, resistance has usually occurred. By selection from a two million entry chemical library based on the efficacy and safety, we identified purine-type compounds that were active against lung small cell lung cancer (NSCLC). The purine compound 5a (GRC0321) was an MTA with good effects against NSCLC. Lung cancer cells H1975 treated with 5a could induce microtubule fragmentation, leading to G2/M cell cycle arrest and intrinsic apoptosis. Compound 5a directly targeted katanin and regulated the severing activity of katanin, which cut the cellular microtubules into short pieces and activated c-Jun N-terminal kinases (JNK). The microtubule fragmenting effect of 5a is a unique mechanism in MTAs. It might overcome the resistance problems that most of the MTAs have faced.

原文English
頁(從 - 到)8521-8534
頁數14
期刊Journal of Medicinal Chemistry
59
發行號18
DOIs
出版狀態Published - 2016 九月 22

指紋

Microtubules
Lung Neoplasms
Cell Death
G2 Phase Cell Cycle Checkpoints
Small Molecule Libraries
katanin
purine
JNK Mitogen-Activated Protein Kinases
Small Cell Lung Carcinoma
Neoplasms
Apoptosis
Safety
Lung
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

引用此文

Kuo, Ting Chun ; Li, Ling Wei ; Pan, Szu Hua ; Fang, Jim Min ; Liu, Jyung Hurng ; Cheng, Ting Jen ; Wang, Chia Jen ; Hung, Pei Fang ; Chen, Hsuan Yu ; Hong, Tse-Ming ; Hsu, Yuan Ling ; Wong, Chi Huey ; Yang, Pan Chyr. / Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin. 於: Journal of Medicinal Chemistry. 2016 ; 卷 59, 編號 18. 頁 8521-8534.
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abstract = "Microtubule targeting agents (MTAs) constitute a class of drugs for cancer treatment. Despite many MTAs have been proven to significantly improve the treatment outcomes of various malignancies, resistance has usually occurred. By selection from a two million entry chemical library based on the efficacy and safety, we identified purine-type compounds that were active against lung small cell lung cancer (NSCLC). The purine compound 5a (GRC0321) was an MTA with good effects against NSCLC. Lung cancer cells H1975 treated with 5a could induce microtubule fragmentation, leading to G2/M cell cycle arrest and intrinsic apoptosis. Compound 5a directly targeted katanin and regulated the severing activity of katanin, which cut the cellular microtubules into short pieces and activated c-Jun N-terminal kinases (JNK). The microtubule fragmenting effect of 5a is a unique mechanism in MTAs. It might overcome the resistance problems that most of the MTAs have faced.",
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Kuo, TC, Li, LW, Pan, SH, Fang, JM, Liu, JH, Cheng, TJ, Wang, CJ, Hung, PF, Chen, HY, Hong, T-M, Hsu, YL, Wong, CH & Yang, PC 2016, 'Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin', Journal of Medicinal Chemistry, 卷 59, 編號 18, 頁 8521-8534. https://doi.org/10.1021/acs.jmedchem.6b00797

Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin. / Kuo, Ting Chun; Li, Ling Wei; Pan, Szu Hua; Fang, Jim Min; Liu, Jyung Hurng; Cheng, Ting Jen; Wang, Chia Jen; Hung, Pei Fang; Chen, Hsuan Yu; Hong, Tse-Ming; Hsu, Yuan Ling; Wong, Chi Huey; Yang, Pan Chyr.

於: Journal of Medicinal Chemistry, 卷 59, 編號 18, 22.09.2016, p. 8521-8534.

研究成果: Article

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AU - Pan, Szu Hua

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AU - Liu, Jyung Hurng

AU - Cheng, Ting Jen

AU - Wang, Chia Jen

AU - Hung, Pei Fang

AU - Chen, Hsuan Yu

AU - Hong, Tse-Ming

AU - Hsu, Yuan Ling

AU - Wong, Chi Huey

AU - Yang, Pan Chyr

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