CDK9-IN-40 is an orally active inhibitor of CDK9, with an IC50 of 5.5 nM. It shows reduced activity against CDK1, CDK2, CDK4, and CDK6. CDK9-IN-40 can arrest the cell cycle, induce apoptosis (cell death), and inhibit tumor growth, demonstrating potent anticancer activity.

CDK9-IN-40 (Compound 8e) demonstrates exceptional inhibitory activity against CDK9 at a concentration of 1.0 μM for 48 hours, achieving 99% inhibition with an IC50 of 5.5 nM. It exhibits selectivity for CDK9 over CDK1 and CDK2 by more than 180 and 75 times, respectively. Furthermore, at concentrations ranging from 1.8 μM to 3.0 μM for 48 hours, CDK9-IN-40 significantly inhibits cell growth in HeLa, A549, HCT116, and MCF-7 cells, with potency equal to or greater than ZK 304709. At concentrations between 1 μM and 4 μM over 24 hours, it causes HCT116 cells to arrest in the G2/M phase and induces apoptosis, exhibiting a concentration-dependent effect.

CDK9-IN-40 (Compound 8e) administered orally at 60 mg/kg once daily for 7 days demonstrated strong in vivo antitumor activity in an HCT116 xenograft mouse model, achieving a tumor growth inhibition rate of 59.2% at this dosage without evident signs of toxicity.