CDK9/HDAC1/HDAC3-IN-1 is a dual inhibitor targeting CDK9 and HDAC enzymes. It potently suppresses the activity of CDK9, HDAC1, and HDAC3, with IC50 values of 0.17 μM, 1.73 μM, and 1.11 μM, respectively. The compound inhibits cancer cell growth by inducing apoptosis and causing cell cycle arrest at the G2/M phase. In a mouse model using TNBC MDA-MB-231 xenografts, it effectively hinders tumor progression. This compound exhibits broad-spectrum anticancer effects, notably against breast cancer, cervical cancer, and liver cancer.

CDK9:0.17 μM(EC50)

CDK9/HDAC1/HDAC3-IN-1 (Compound 13EA) exhibits potent antiproliferative activity across various cancer cell lines, with IC50 values of 1.51 μM in HeLa, 2.47 μM in MDA-MB-231, and 4.52 μM in HepG2 cells. In MDA-MB-231 cells at concentrations ranging from 0.625 to 5 μM over 24 hours, it suppresses p-Ser2 mRNA expression in a time- and dose-dependent manner. Additionally, CDK9/HDAC1/HDAC3-IN-1 significantly reduces p-Ser2 (a substrate of CDK9) protein expression while increasing Ac-H3 (a substrate of HDAC) protein levels in both MDA-MB-231 and HeLa cells. The compound, at concentrations of 0.625 to 5 μM over 24 hours, induces concentration-dependent mitochondrial apoptosis, elevates cleaved PARP expression, and causes cell cycle arrest at the G2/M phase in MDA-MB-231 and HeLa cells.

CDK9/HDAC1/HDAC3-IN-1, administered via intraperitoneal injection at a dosage of 30 mg/kg once daily for 10 days, significantly inhibits tumor growth in the MDA-MB-231 xenograft mouse model.