PLK1-IN-16

PLK1-IN-16 is a selective inhibitor of polo-like kinase 1 (PLK1) with an IC50 of 0.25 nM. It exhibits lower inhibitory activity against PLK2 and PLK3, induces G2 phase cell cycle arrest, and triggers apoptosis (apoptosis), showing antiproliferative activity in tumor cells. The compound is stable under simulated gastric acid conditions and has an acceptable level of CYP 450 inhibition. PLK1-IN-16 is applicable for research in triple-negative breast cancer (TNBC), breast cancer, and leukemia.

PLK1:0.25 nM

PLK1-IN-16 (compound B7) effectively inhibits the proliferation of MDA-MB-231, MDA-MB-361, and MV-4-11 cells with IC₅₀ values of 72.5 nM, 316 nM, and 32.1 nM, respectively. When applied at concentrations of 12.5-200 nM for 72 hours, it induces a dose-dependent G2 phase arrest in MV-4-11 cells. Additionally, PLK1-IN-16 at 5.0-80.0 nM over 72 hours triggers apoptosis in MV-4-11 cells in a dose-dependent manner. The compound remains stable under simulated gastric acid conditions with a residual rate of 98.4% after 2 hours. PLK1-IN-16 exhibits weak inhibition of CYP1A2, CYP2C9, CYP2C19, and CYP2D6, while strongly inhibiting CYP3A4 with an IC₅₀ of approximately 1 μM. It demonstrates high plasma protein binding rates of 99.6% in humans, 99.7% in rats, and 99.4% in mice.

PLK1-IN-16 (compound B7) administered at 20 mg/kg orally in a single dose exhibits a high safety profile in mice, with no significant physiological abnormalities or pathologies observed in the heart, liver, spleen, lungs, or kidneys, and normal growth and development maintained.