Grennady Wirjanata, Jianqing Lin, Jerzy Michal Dziekan, Abbas El Sahili, Zara Chung, Seth Tjia, Nur Elyza Binte Zulkifli, Josephine Boentoro, Roy Tham, Lai Si Jia, Ka Diam Go, Han Yu, Anthony Partridge, David Olsen, Nayana Prabhu, Radoslaw M Sobota, Pär Nordlund, Julien Lescar, Zbynek Bozdech
Identification of new druggable protein targets remains the key challenge in the current antimalarial development efforts. Here we used mass-spectrometry-based cellular thermal shift assay (MS-CETSA) to identify potential targets of several antimalarials and drug candidates. We found that falcilysin (FLN) is a common binding partner for several drug candidates such as MK-4815, MMV000848, and MMV665806 but also interacts with quinoline drugs such as chloroquine and mefloquine. Enzymatic assays showed that these compounds can inhibit FLN proteolytic activity...
April 5, 2024: Cell Chemical Biology