Biochemical and cellular effects of a novel cyclin-dependent kinase inhibitor

The antiproliferative activity of LGR1404 was verified by flow cytometric analysis of asynchronously growing breast cancer cell line MCF-7 and multiple myeloma cell line RPMI-8226 cells doubly stained with propidium iodide and 5-bromo-2'-deoxyuridine (BrdU). As shown in Figure 5 both studied inhibitors arrested cancer cell lines in G /M phases and decreased size of 2 their S-phase populations. Upon treatment with higher concentration of roscovitine and LGR1404 markedly decreased population of cells actively replicating DNA (i.e. BrdU-positive cells). In addition, in RPMI-8226 cells was observed partially accumulation G phase population, but this 1 tendency was not observed in MCF-7 cells. LGR1404 showed the same tendency in cell cycle arrest comparable with roscovitine which blocks G /S and G /M transition, but studied 1 2 pyrazolo[4,3-d]pyrimidine is more efficient.