体外研究
(In Vitro) | R547 effectively inhibits CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1 (Ki = 1–3 nmol/L) and is inactive (Ki >5,000 nmol/L) against a panel of >120 unrelated kinases in cell-free assays[4].
R547 effectively inhibits the proliferation of tumor cell lines independent of multidrug resistant status, histologic type, retinoblastoma protein, or p53 status, with IC50s<0.60 μM[4].
R547 reduces phosphorylation of the cellular retinoblastoma protein at specific CDK phosphorylation sites at the same concentrations that induced cell cycle arrest[4].
R547 has anti-proliferative activity in tumor cells independent of p53, retinoblastoma, or MDR status[4].
R547 blocks tumor cells in G1 plus G2 and induces apoptosis[4].
R547 induces apoptosis as measured by DNA fragmentation[4].
R547 inhibits phosphorylation of retinoblastoma protein in humantumor cells[4].
Cell Cytotoxicity Assay[4] | Cell Line: | Human tumor cell lines (MDA-MB-468, MDA-MB-435, MCF-7, HCT116, SW480, RKO, HT-29, HCT15, H460a, C33A, DU145, OSA-CL, LOX, JEKO-1, REC-1) | | Concentration: | MTT assay | | Incubation Time: | 5 days | | Result: | Has potent in vitro antiproliferative activity. |
Cell Cycle Analysis[4] | Cell Line: | R547, HCT116 | | Concentration: | 0.1 μM, 0.2 μM, 0.6 μM | | Incubation Time: | 20 hours | | Result: | Decrease in BrdUrd incorporation and in percentage S phase in a dose-dependent, indicative of a cell cycle block in G1-S plus G2-M. |
Western Blot Analysis[4] | Cell Line: | HCT116 cells | | Concentration: | 0.1 μM, 0.2 μM, 0.6 μM | | Incubation Time: | 24 hours, 48 hours, 72 hours | | Result: | Showed a band corresponding to a p48/retinoblastoma fragment that becomes more intense at 48 and 72 hours. |
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