Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK)

Highlights • We discovered novel ALK PROTACs (MS4077 and MS4078) and their close analogs as negative controls. • MS4077 and MS4078 potently reduced cellular ALK protein levels in a cereblon and proteasome dependent manner. • MS4077 and MS4078 potently inhibited cellular ALK signaling. • MS4077 and MS4078 effectively inhibited cancer cell proliferation. • MS4078 displayed good plasma exposure in mice, thus is suitable for in vivo efficacy studies. READ ARTICLE

European Journal of Medicinal Chemistry DOI: 10.1016/j.ejmech.2018.03.071

Authors: Chengwei Zhang, Xiao-RanHan, Xiaobao Yang, Biao Jiang, Jing Liu, Yue Xiong, Jian Jin

Pre-ClinicalKirk SmithMay 10, 2018PROTAC, Protein degrader, ALK, Lymphoma, Lung cancer