PLK1-IN-13 is a selective, orally active PLK1 inhibitor with an IC50 of 0.27 nM. It also inhibits PLK2 (IC50: 12.72 nM) and PLK3 (IC50: 4.12 nM). PLK1-IN-13 induces cell cycle arrest at the G2 phase, promotes apoptosis, and downregulates the transcription of the cancer-associated oncogene c-MYC. This compound inhibits tumor growth and is applicable for research in acute myeloid leukemia (AML).

PLK1:0.27 nM

PLK1-IN-13 (72 h) (Compound WD6) exhibits antiproliferative effects on MDA-MB-231 (IC 50: 9.5 nM) and MV4-11 cells (IC 50: 23.3 nM) and has IC 50 values of 47.1 nM and 59.9 nM for MCF-7 and HCT-116, respectively. It weakly inhibits CYP2C9 (IC 50: 7.39 μM), CYP2C19 (IC 50: 14 μM), CYP2D6 (IC 50: 13.8 μM), and CYP3A4 (IC 50: 17.3 μM), suggesting a low potential for drug-drug interactions. Additionally, PLK1-IN-13 induces G2/M cell cycle arrest and apoptosis in MV4-11 cells at concentrations ranging from 2.92 nM to 46.6 nM over 72 hours and downregulates the transcription of the proliferation-associated oncogene c-MYC in MV4-11 cells within 24 hours at 0-1 μM concentrations.

PLK1-IN-13 (Compound WD6) administered orally at 20 mg/kg once daily for 19 consecutive days significantly inhibits tumor growth in MV4-11 xenograft mouse models, achieving a tumor growth inhibition (TGI) of 91.2%. Additionally, PLK1-IN-13 (administered orally at 10 and 20 mg/kg) exhibits a favorable half-life, high plasma exposure, and moderate bioavailability in SD rats.