Figure 3
There is no modulation of Pgp or BCRP function by barasertib-hQPA. A, R123 accumulation in OCI-AML3DNR cells +/- 300 nM barasertib-hQPA (i) or 2.5 μg/ml CSA (ii). The dotted lines are the 4°C R123 control. The solid black line is R123 + diluent control and the solid grey line R123 + barasertib-hQPA (i) and R123 + CSA (ii). B, BODIPY-prazosin accumulation in OCI AML6.2 cells +/- 300 nM barasertib-hQPA (i) or 10 μM FTC (ii). The dotted lines are the 4°C BODIPY control. The solid black line is BODIPY + diluent control and the solid grey line BODIPY + barasertib-hQPA (i) and BODIPY + FTC (ii). Plots are representative of a single experiment which was done in triplicate. C, UIC2 binding in KG-1a cells in the presence of 5 μM vinblastine (i), 1 μM barasertib-hQPA (ii) or a combination of both (iii). The dark filled line is the diluent control and the light line indicates any shift. D, 300nM [14C]-barasertib-hQPA uptake in Pgp expressing OCI-AML3DNR cells +/- the Pgp modulator CSA and in OCI-AML6.2 cells +/- the BCRP modulator FTC. Pgp/BCRP negative OCI-AML3 cells have been used as a positive control (*p = 0.004/**p = 0.005) (analysed using paired samples t-test), +95% confidence interval). Diluent controls were included for each modulator. Columns, mean of three experiments; bars, SD.