The reactions were conducted in 50-μL volumes in 96-well plates and contained 1.3 nM wild-type or 0.5 nM mutant ALK, 3 μM phosphoacceptor peptide (5′FAM-KKSRGDYMTMQIG-CONH2, synthesized by CPC Scientific, Sunnyvale, CA)..

Abstract

Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS positive patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine 8e, which was potent across a broad panel of engineered ALK mutant cell lines and showed suitable preclinical pharmacokinetics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).

SOCIAL MEDIA

Connect with us and stay updated by following our social media channels.

Latest Briefings from our Knowledge Center

Press Releases, Industry News, Articles, and Technical Content

Contact Us