Wee1/HDAC-IN-1 is a dual inhibitor targeting Wee1 and HDACs, exhibiting IC50 values of 1.2 nM for Wee1, 196 nM for HDAC1, 156 nM for HDAC3, and 55 nM for HDAC6. It shows potent antiproliferative activity against MV4-11 cells, with an IC50 of 0.076 μM. This compound selectively binds to the catalytic sites of Wee1 and HDACs, disrupting DNA damage repair pathways and inducing apoptosis in MV4-11 cells (apoptosis). Wee1/HDAC-IN-1 is applicable for studying acute myeloid leukemia.

Wee1:1.2 nM

Wee1/HDAC-IN-1 (Compound 23f) exhibits potent antiproliferative activity across various types of AML cells over 72 hours. The compound shows IC50 values of 0.076 μM for MV4-11 cells, 0.773 μM for THP-1 cells, and 0.309 μM for HL-60 cells. Additionally, Wee1/HDAC-IN-1 (10-75 nM; 96 h) demonstrates the ability to induce differentiation in MV4-11 cells. At concentrations of 37.5-600 nM for 72 hours, the compound induces apoptosis in MV4-11 cells in a dose-dependent manner. Moreover, Wee1/HDAC-IN-1 (19-1200 nM; 72 h) reduces CDK1 phosphorylation levels and increases acetylation of histone H3 in a dose-dependent fashion. It can also promote the expression of γH2A.X, a marker of DNA double-strand breaks, in a dose-dependent manner.

The compound Wee1/HDAC-IN-1 (Compound 23f) administered at a dose of 15-60 mg/kg via intraperitoneal injection once daily for 21 days inhibits the growth of tumors created by subcutaneous injection of MV4-11 cells in BALB/c nude mice. At a dose of 150 mg/kg through a single tail vein injection, Wee1/HDAC-IN-1 demonstrates an acceptable hepatic and renal safety profile in ICR mice (18-20 g).