BI 2536

PLK2:3.5 nM (cell free)|PLK1:0.83 nM (cell free)|PLK3:9 nM (cell free)

BI 2536 inhibits growth of human tumor xenografts in nude mice and induces regression of large tumors with well-tolerated intravenous dose regimens. In treated tumors, cells arrest in prometaphase, accumulate phosphohistone H3, and contain aberrant mitotic spindles [1].

BI 2536 inhibits Plk1 enzyme activity at low nanomolar concentrations. The compound potently causes a mitotic arrest and induces apoptosis in human cancer cell lines of diverse tissue origin and oncogenome signature [1]. On treatment with nanomolar doses of BI 2536, ATC cells progressed normally through S phase but died thereafter, directly from mitotic arrest. Nontransformed thyroid cells were 3.2- to 18.4-fold less susceptible to BI 2536-induced cell cycle effects compared with ATC cells [2].

H2O:<1 mg/mL,Ethanol:93 mg/mL (178.3 mM),DMSO:20 mg/mL (38.3 mM)

Cell proliferation assays were performed by incubation in the presence of various concentrations of BI 2536 for 72 hr, and cell growth was assessed by the measurement of Alamar Blue dye conversion in a fluorescence spectrophotometer. Effective concentrations at which cellular growth was inhibited by 50% (EC50) were extrapolated from the dose-response curve fit [1].

Female BomTac:NMRI-Foxn1nu mice were grafted subcutaneously with HCT 116 colon-carcinoma, NCI-H460, or A549 lung carcinoma cells by subcutaneous injection, respectively, of 2 × 10^6, 1 × 10^6, and 1 × 10^7 cells into the flank of each mouse. When tumors reached a volume of approximately 50 mm^3, animals were pair-matched into treatment and control groups of ten mice each. In regression experiments, treatment was not initiated until the mean tumor volume reached 500 mm^3. BI 2536 was formulated in hydrochloric acid (0.1 N), diluted with 0.9% NaCl, and injected intravenously into the tail vein at the indicated dose and schedule. The administration volume was 10 ml per kg body weight. Tumor volumes were determined three times a week with a caliper. The results were converted to tumor volume (mm^3) by the following formula: length × width2 × π/6. The weight of the mice was determined as an indicator of tolerability on the same days. For statistical analysis, the treatment group was compared with the vehicle control group in a one-sided (decreasing) exact Wilcoxon test [1].