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vu661013 is a novel, potent, selective mcl-1 inhibitor (ki of 97 ± 30 pm).[1]mcl-1, an anti-apoptotic bcl-2 family member, is commonly upregulated in acute myeloblastic leukemia (aml) cells. targeting anti-apoptotic proteins in aml is a key therapeutic strategy, and mcl-1 is a critical anti-apoptotic oncoprotein. [1]vu661013 reduced expansion of multiple aml cell lines in vitro. venetoclax (a bcl-2 inhibitor) and vu661013 exhibited favorable synergy in several of aml cells lines, venetoclax-resistant aml cells were sensitive to vu661013. [1]vu661013 decreased tumor growth in an in vivo murine model. vu661013 (25mg/kg) and venetoclax (15mg/kg) can be synergistic in patient-derived xenograft transplantation models. [1][1]a novel mcl-1 inhibitor combined with venetoclax rescues venetoclax resistant acute myelogenous leukemia. cancer discov. 2018 sep 5. pmid: 30185627. doi: 10.1158/2159-8290.cd-18-0140

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