CDK/HDAC-IN-3 is an orally active dual inhibitor of HDACs and CDKs, offering potent and selective inhibition of CDK9, CDK12, CDK13, HDAC1, HDAC2, and HDAC3, with IC50 values of 98.32 nM, 98.85 nM, 100 nM, 62.12 nM, 93.28 nM, and 82.87 nM, respectively, and is applicable in the treatment of acute myeloid leukemia (AML) [1].

CDK/HDAC-IN-3 (compound 33a) at 1 μM demonstrates potent and selective inhibition of CDK9, CDK12, CDK13, HDAC1, HDAC2, and HDAC3 with IC50 values of 98.32 nM, 98.85 nM, 100 nM, 62.12 nM, 93.28 nM, and 82.87 nM, respectively [1]. At 0.5 μM and 1.0 μM, this compound significantly induces the differentiation of leukemia stem cell-like cells and inhibits AML proliferation [1]. Additionally, at 0.5 μM, 1.0 μM, and 2.0 μM, CDK/HDAC-IN-3 markedly promotes the differentiation of LSCs [1]. The compound also exhibits inhibitory effects on U937, HL-60, SKNO-1, and Kasumi-1 cells with IC50 values of 0.72 μM, 1.43 μM, 1.63 μM, and 0.89 μM, respectively [1].

CDK/HDAC-IN-3 (compound 33a) demonstrates good oral bioavailability when administered intravenously (i.v.) at 5 mg/kg and orally (p.o.) at 25 mg/kg [1].