biostudies-literatureUnknown42(4)Yu MThe kinase FLT3 internal tandem duplication (FLT3-ITD) is related to poor clinical outcomes of acute myeloid leukemia (AML). FLT3 inhibitors have provided novel strategies for the treatment of FLT3-ITD-positive AML. But they are limited by rapid development of acquired resistance and refractory in monotherapy. Recent evidence shows that inducing the degradation of FLT3-mutated protein is an attractive strategy for the treatment of FLT3-ITD-positive AML, especially those with FLT3 inhibitor resistance. In this study we identified Wu-5 as a novel USP10 inhibitor inducing the degradation of FLT3-mutated protein. We showed that Wu-5 selectively inhibited the viability of FLT3 inhibitor-sensitive (MV4-11, Molm13) and -resistant (MV4-11R) FLT3-ITD-positive AML cells with IC₅₀ of 3.794Acta pharmacologica Sinica604-612https://www.ebi.ac.uk/biostudies/studies/S-EPMC8115260biostudies-literatureWu-5, a novel USP10 inhibitor, enhances crenolanib-induced FLT3-ITD-positive AML cell death via inhibiting FLT3 and AMPK pathways.PMC8115260Yu MLiu MLei HBu ZLXiao XHWu YLLiu WZhang ZLZhang YCao YXu HZWang WWZhang XMWang YYWu YZFang ZXfalseWu-5, a novel USP10 inhibitor, enhances crenolanib-induced FLT3-ITD-positive AML cell death via inhibiting FLT3 and AMPK pathways.The kinase FLT3 internal tandem duplication (FLT3-ITD) is related to poor clinical outcomes of acute myeloid leukemia (AML). FLT3 inhibitors have provided novel strategies for the treatment of FLT3-ITD-positive AML. But they are limited by rapid development of acquired resistance and refractory in monotherapy. Recent evidence shows that inducing the degradation of FLT3-mutated protein is an attractive strategy for the treatment of FLT3-ITD-positive AML, especially those with FLT3 inhibitor resistance. In this study we identified Wu-5 as a novel USP10 inhibitor inducing the degradation of FLT3-mutated protein. We showed that Wu-5 selectively inhibited the viability of FLT3 inhibitor-sensitive (MV4-11, Molm13) and -resistant (MV4-11R) FLT3-ITD-positive AML cells with IC₅₀ of 3.7942021-01-01T00:00:00Z2021 Apr2025-04-29T11:33:24.847Z2025-04-06T19:54:40.473ZS-EPMC81152603269475710.1038/s41401-020-0455-x