PLK1-IN-13

PLK1-IN-13 is a selective and orally active PLK1 inhibitor ( IC₅₀: 0.27 nM). PLK1-IN-13 also inhibits PLK2 (IC₅₀: 12.72 nM) and PLK3 (IC₅₀: 4.12 nM). PLK1-IN-13 arrests cell at G2 phase, induces apoptosis and down-regulates the transcription of the proliferation-related oncogene c-MYC. PLK1-IN-13 inhibits tumor growth, and can be used for research of acute myeloid leukemia (AML) ^[1].

In Vivo, PLK1-IN-13 (Compound WD6) (20 mg/kg, p.o., once a day for 19 consecutive days) inhibits the tumor growth (TGI = 91.2 %) in xenograft mouse models of MV4-11^[1]. PLK1-IN-13 (10, 20 mg/kg, i.g.) shows a good half-life, high plasma exposure, and moderate bioavailability in SD rats^[1].

In Vitro, PLK1-IN-13 (Compound WD6) (72 h) has antiproliferative activities against MDA-MB-231 (IC₅₀: 9.5 nM) and MV4-11 cell (IC₅₀: 23.3 nM), and the IC₅₀ for MCF-7 and HCT-116 are 47.1 nM and 59.9 nM respectively^[1]. PLK1-IN-13 has weak inhibitory effects on CYP2C9 (IC₅₀: 7.39 μM), CYP2C19 (IC₅₀: 14 μM), CYP2D6 (IC₅₀: 13.8 μM), and CYP3A4 (IC₅₀: 17.3 μM), indicating that PLK1-IN-13 may have lower drug-drug interactions^[1]. PLK1-IN-13 (2.92 nM-46.6 nM, 72 h) induces G2/M cell-cycle arrest and induces apoptosis in MV4-11 cells^[1]. PLK1-IN-13 (0-1 μM, 24 h) down-regulates the transcription of the proliferation-related oncogene c-MYC in MV4-11 cells^[1].

References:
[1]. Hou Y, et al. Discovery of novel dihydropteridone derivatives as orally bioavailable PLK1 inhibitors with reduced hERG inhibitory activity for acute myeloid leukemia treatment. Eur J Med Chem. 2025 May 5;289:117480.