CDK9-IN-42 is a potent and selective CDK9 inhibitor with an IC50 value of 3.8 nM. It inhibits cancer cell growth and induces apoptosis by downregulating Myc-1 and c-Myc. CDK9-IN-42 is applicable in cancer research, including studies on breast cancer and lung cancer.

CDK9:3.8 nM

CDK9-IN-42 (Compound L18) effectively inhibits the proliferation of various hematological tumor cells with IC50 values for MV4-11, MOLM-13, THP-1, KG-1, and HL-60 cells at 0.049 μM, 0.071 μM, 0.062 μM, 0.093 μM, and 0.175 μM, respectively. It also suppresses the growth of multiple solid tumor cells, achieving IC50 values of 0.045 μM for HepG2, 0.166 μM for MCF-7, 0.247 μM for 22RV1, and 0.225 μM for A549 cells. Exhibiting low cytotoxicity on normal human bronchial epithelial cells, it has an IC50 of 0.402 μM for BEAS-2B cells. CDK9-IN-42 demonstrates excellent selectivity for CDK9 over other CDK family members, with IC50 values exceeding 1 μM for CDK1, CDK4, CDK6, and CDK7. It can downregulate protein levels of p-RNAPII-ser2, Mcl-1, c-Myc, CDK9, and cyclin T1 in MV4-11 cells at concentrations of 0.1-0.5 μM within 12 hours, and induces apoptosis in MV4-11 cells at 0.5-1 μM over 12 hours.

Administered as a single intravenous dose, CDK9-IN-42 (Compound L18) at 15-50 mg/kg did not result in mortality or significant weight loss in ICR mice.