美国进口，现货，BI 2536，目录号S1109 ，CAS号:755038-02-9, 876126-71-5 (H2O)，细胞周期(Cell Cycle / Checkpoint) ， PLK YZ剂，美国Selleck

Comparison between Genetic Ablation of Cdc20 and Current Mitotic Drugs (C) Transformed Cdc20(lox/lox); RERT(+/Cre) MEFs were subcutaneously injected into the two flanks of SCID mice, and tumors were scored every 2–3 days.These mice were injected i.p. (three injections per week) with 4-OHT or mitotic drugs (taxol, vincristine, and BI2536) when tumors reached about 200 mm3 of volume (day 11; arrow) (n = 8 mice per group). (D) Representative images of these fibrosarcomas 3 days after injection with 4-OHT (to generate Cdc20(D/D) cells), BI2536, or taxol. These mice were injected with 10 mM BrdU to score DNA replication. CA3, immunodetection of active caspase 3. Scale bars, 50 or 10 mM (insets).

Treatment with BI 2536 induces cell-cycle arrest in NB TICs and aberrant accumulation of cyclin B1 and p21. C, expression of cyclin B1 and p21 was assessed in NB88R2 following 16 and 24-hour treatment with different doses of BI 2536 (10, 30, and 100 nmol/L). ERK1 (extracellular signal regulated kinase 1) was used as the loading control. D, inhibition of PLK1 was assessed by in vitro kinase assay following treatment of NB88R2 for 3 hours with BI 2536.

Treatment with BI 2536 induces cell death via apoptosis. A,treatment with BI 2536 (10, 30, and 100 nmol/L) reduces viable cell numbers as assessed by trypan blue exclusion. B, representative Western blot demonstrating accumulation of cleaved PARP following treatment with 10 nmol/L BI 2536 .

BI 2536 inhibits NB tumor growth in vivo. A and B, NOD/SCID mice bearing 50- to100-mm3 tumors were injected intravenously with either vehicle (0.1N HCl per saline) or 12.5 to 25mg/kg BI 2536 for 2 consecutive days a week, for a total of 3 cycles.Two independent experiments were performed in each case with 5 animals per group. Representative tumor growth data are shown.

animals with 50- to 100-mm3 tumors were randomized into 4 groups: group 1 injected intravenously with vehicle (0.1N HCl per saline), group 2 injected intravenously with 12.5 mg/kg of BI 2536 (2 consecutive days, 3 cycles), group 3 injected i.p. with 10 mg/kg of irinotecan (3 doses total, 3 days apart), and group 4 injected with BI 2536 and irinotecan. Both representative tumor growth data and a Kaplan–Meyer survival plot are shown.