Figure 1.

The accumulation and retention of [¹⁴C]rucaparib, associated durable PARP inhibition in human cancer cell lines and cytotoxicity to BRCA 1 and 2 mutant cells. (A) Michaelis–Menten kinetics of rucaparib accumulation in SW620 cells, exposed to increasing rucaparib concentrations for 30 min before determination of intracellular concentration data are for a single representative experiment. (B–E) Rucaparib accumulation in the presence of various transporter inhibitors: Na+/K+ ATPase inhibitor Ouabain at 30 and 100 μM (B); the glucose transport inhibitor, cytochalasin B at 0.1 and 1 μM (C); the nucleoside transport inhibitor, dipyridamole at 10 and 100 μM (D); and the amino-acid transport inhibitor BCH at 1 or 2 mM (E). (F) Time course of uptake and retention of [¹⁴C]rucaparib in SW620 cells exposed to 400 nM [¹⁴C]rucaparib for 20 min before washing and incubating in fresh medium for a further 2 h, data are from triplicate estimations in a single representative experiment.