Article
Discovery of Oral Degraders of the ROS1 Fusion Protein with Potent Activity against Secondary Resistance Mutations.
Journal of medicinal chemistry - 24 Oct 2024
Peng Xianyou, Guo Shanchun, Zheng Shilong, Hossain Ahamed, Zhang Changde, Mottamal Madhusoodanan, Skripnikova Elena, Ma Peng, Martinez-Carter Kindy, Zhang Qiang, Abedin Faisal, Huckaba Thomas, Wang Guangdi
Abstract excerpt
The development of therapeutic resistance in the majority of patients limits the long-term benefit of ROS1 inhibitor treatment. On-target mutations of the ROS1 kinase domain confer resistance to crizotinib and lorlatinib in more than one-third of acquired resistance cases with no current effective treatment option. As an alternative to stoichiometric inhibition, proteolytic degradation of ROS1 could provide an...
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