New Thalidomide-Resembling Dicarboximides Target ABC50 Protein and Show Antileukemic and Immunomodulatory Activities.

ABSTRACT: We identified novel dicarboximides that were selectively cytotoxic towards human leukemia cells. Using chemical and biological methods, we characterized the biological activity, identified cellular protein targets and defined the mechanism of action of the test dicarboximides. The reported IC₅₀ values (concentration required to reduce cell survival fraction to 50% of control) of selected dicarboximides were similar or lower than IC₅₀ of registered anticancer drugs, for example cytarabine, sorafenib, irinotecan. Test compounds induced apoptosis in chronic myelogenous (K562) and acute lymphoblastic (MOLT-4) leukemia cells by activation of receptor and mitochondrial apoptotic pathways and increased the expression of proapoptotic genes (BAX, NOXA, HTRA2, TNFRSF10B, ESR

SUBMITTER: Cieslak M 

PROVIDER: S-EPMC6770581 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature