Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Nov 26, 2015; 6(4): 409-418
Published online Nov 26, 2015. doi: 10.4331/wjbc.v6.i4.409
JAK3 inhibitor VI is a mutant specific inhibitor for epidermal growth factor receptor with the gatekeeper mutation T790M
Naoyuki Nishiya, Yasumitsu Sakamoto, Yusuke Oku, Takamasa Nonaka, Yoshimasa Uehara
Naoyuki Nishiya, Yusuke Oku, Yoshimasa Uehara, Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmacy, Yahaba, Iwate 028-3694, Japan
Yasumitsu Sakamoto, Takamasa Nonaka, Department of Structural Biology and Biophysics, Iwate Medical University School of Pharmacy, Yahaba, Iwate 028-3694, Japan
Author contributions: Nishiya N, Nonaka T and Uehara Y designed the research; Nishiya N and Sakamoto Y performed the research; Nishiya N, Sakamoto Y and Oku Y analyzed the data; Nishiya N and Sakamoto Y wrote the paper.
Conflict-of-interest statement: None of the authors have financial conflicts related to this work.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Naoyuki Nishiya, PhD, Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmacy, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan. nnishiya@iwate-med.ac.jp
Telephone: +81-19-6515111 Fax: +81-19-6981841
Received: May 27, 2015
Peer-review started: May 30, 2015
First decision: June 18, 2015
Revised: July 22, 2015
Accepted: September 10, 2015
Article in press: September 16, 2015
Published online: November 26, 2015
Processing time: 179 Days and 14.7 Hours
Core Tip

Core tip: Non-small cell lung cancers caused by mutations in the epidermal growth factor receptor (EGFR) initially respond to tyrosine kinase inhibitors (TKIs). However, the therapeutic efficacy of EGFR-TKIs is limited by drug-resistant mutations such as the gatekeeper mutation T790M. Our present study rediscovered JAK3 inhibitor VI, a known TKI for Janus kinases (JAKs), as a selective EGFR T790M inhibitor. Our structural analysis revealed similarities among EGFR T790M and JAKs, offering a possible strategy to search for EGFR T790M inhibitors from known kinase inhibitors. Repositioning of the existing therapeutics may facilitate solving clinical problems such as drug resistance and toxicity.