Fig. 2: ATR-CHK1 pathway activation by rucaparib is inhibited by VE-821, PF-477736 and MK-1775. | British Journal of Cancer

Fig. 2: ATR-CHK1 pathway activation by rucaparib is inhibited by VE-821, PF-477736 and MK-1775.

From: ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors

Fig. 2

a Cells were exposed to DMSO, 10 µM rucaparib alone or in the presence of 1 µM VE-821, 50 nM PF-477736, 200 nM PF-477736, 100 nM MK-1775 or 300 nM MK-1775 for 24 h prior to lysis. N.B. Since the phosphorylation in the absence of activation by rucaparib is very low such that inhibition by VE-821, PF-477736, and MK-1775 would be difficult to measure with any accuracy the effect of the inhibitors was only evaluated in the presence of rucaparib. Representative Western blot of UWB and UWB+ B1 cells are shown b–d Levels of pCHK1 S345, pCHK1 S296 and pCDK1 Y15 were measured by densitometry and normalised to relative vinculin loading control. Fold-change in expression (determined by densitometry) from DMSO control cells to cells treated with rucaparib +/- kinase inhibitors is shown. Data shown are mean and standard error of 3 independent experiments.

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