Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance

We discovered lorlatinib-resistant multiple ALK-compound mutations and an L1256F single mutation as well as the potential therapeutic strategies for these ALK mutations. Our original computational simulation to calculate the binding affinity may be applicable for predicting resistant mutations and for overcoming drug resistance in silico. READ ARTICLE

EBioScience DOI: 10.1016/j.ebiom.2019.01.019

Authors: Koutaroh Okada, Mitsugu Araki, Takuya Sakashita, Biao Ma, Ryo Kanada, Noriko Yanagitani, Atsushi Horiike, Sumi Koike, Tomoo Oh-hara, Kana Watanabe, Keiichi Tamai, Makoto Maemondo, Makoto Nishio, Takeshi Ishikawa, Yasushi, Okuno, Naoya Fjita, Ryohei Katayama

Pre-ClinicalKirk SmithALK-rearranged lung cancer, Resistant mutation, Computational simulation, MP, CAFEE, Compound mutation, Quantum chemistry