Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin KuoTing-Chun LiLing-Wei PanSzu-Hua FangJim-Min LiuJyung-Hurng ChengTing-Jen WangChia-Jen HungPei-Fang ChenHsuan-Yu HongTse-Ming HsuYuan-Ling WongChi-Huey YangPan-Chyr 2016 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 <b>5a</b> (GRC0321) was an MTA with good effects against NSCLC. Lung cancer cells H1975 treated with <b>5a</b> could induce microtubule fragmentation, leading to G2/M cell cycle arrest and intrinsic apoptosis. Compound <b>5a</b> 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 <b>5a</b> is a unique mechanism in MTAs. It might overcome the resistance problems that most of the MTAs have faced.