Hatcher, John M. Bahcall, Magda Choi, Hwan Geun Gao, Yang Sim, Taebo George, Rani Jaenne, Pasi A. Gray, Nathanael S. 2024-01-20T05:31:13Z 2024-01-20T05:31:13Z 2021-09-03 2015-12-10 0022-2623 https://pubs.kist.re.kr/handle/201004/124632 The treatment of patients with advanced non-small-cell lung cancer harboring chromosomal rearrangements of anaplastic lymphoma kinase (ALK) has been revolutionized by the development of crizotinib, a small-molecule inhibitor of ALK, ROS1, and MET. However, resistance to crizotinib inevitably develops through a variety of mechanisms, leading to relapse both systemically and in the central nervous system (CNS). This has motivated the development of "second-generation" ALK inhibitors, including alectinib and ceritinib, that overcome some of the mutations leading to resistance. However, most of the reported ALK inhibitors do not show inhibition of the G1202R mutant, which is one of the most common mutations. Herein, we report the development of a structural analogue of alectinib (JH-VIII-157-02) that is potent against the G1202R mutant as well as a variety of other frequently observed mutants. In addition, JET-VIII-157-02 is capable of penetrating the CNS of mice following oral dosing. English AMER CHEMICAL SOC CELL LUNG-CANCER ACTIVATING MUTATIONS ALK REARRANGEMENTS TYROSINE KINASE CRIZOTINIB NEUROBLASTOMA IDENTIFICATION CHEMOTHERAPY EXPRESSION RECEPTOR Discovery of Inhibitors That Overcome the G1202R Anaplastic Lymphoma Kinase Resistance Mutation Article 10.1021/acs.jmedchem.5b01136 1 JOURNAL OF MEDICINAL CHEMISTRY, v.58, no.23, pp.9296 - 9308 JOURNAL OF MEDICINAL CHEMISTRY 58 23 9296 9308 scie scopus 000366340000016 2-s2.0-84949921074 Chemistry, Medicinal Pharmacology & Pharmacy Article CELL LUNG-CANCER ACTIVATING MUTATIONS ALK REARRANGEMENTS TYROSINE KINASE CRIZOTINIB NEUROBLASTOMA IDENTIFICATION CHEMOTHERAPY EXPRESSION RECEPTOR ALK