YX0798 inhibits CDK9 activity and potently kills MCL cells. (A) YX0798 potently inhibited cell viability of MCL cells (n = 4) at 72 hours after treatment, but not PBMCs from healthy donors (n = 3). (B) The doses of YX0798 used to treat PBMCs were 2.5-fold (100 nM) and fivefold (200 nM) of the average IC₅₀ value of JeKo-1, Mino, and Z138 cells. (C) YX0798 inhibited cell viability and induced apoptosis in a dose-dependent manner at 20 hours after treatment. (D) YX0798 treatment for 6 hours inhibited CDK9 phosphorylation and induced cl of PARP and caspase-3, as well as MCL-1 depletion in a dose-dependent manner. (E) The effects of YX0798 on protein profiling in CDK9 pathways and apoptosis pathways upon treatment for 6 hours. AZD4573 serves as a positive control. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. cl, cleavage; IC₅₀, 50% inhibitory concentration; ns, not significant; p-CDK9; phosphorylated cyclin-dependent kinase 9; p-Rb, phosphorylated retinoblastoma protein; PBMC, peripheral blood mononuclear cell; Rb, retinoblastoma protein.