| Literature DB >> 27536893 |
Ting-Chun Kuo1, Ling-Wei Li2, Szu-Hua Pan1,3,4, Jim-Min Fang2, Jyung-Hurng Liu5,6,7,8, Ting-Jen Cheng9, Chia-Jen Wang10,11, Pei-Fang Hung10, Hsuan-Yu Chen12, Tse-Ming Hong13, Yuan-Ling Hsu3, Chi-Huey Wong9, Pan-Chyr Yang14,15.
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.Entities:
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Year: 2016 PMID： 27536893 DOI： 10.1021/acs.jmedchem.6b00797
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446