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. Author manuscript; available in PMC: 2009 Sep 21.
Published in final edited form as: J Med Chem. 2008 Aug 5;51(16):5052–5063. doi: 10.1021/jm8003366

Figure 5. Competitive inhibition of RFC transport and FR binding activities by 6-substituted pyrrolopyrimidines.

Figure 5

Panel A: PC43-10 cells ectopically expressing wild type RFC but no FR31 were assayed for [3H]MTX in the presence of the pyrrolopyrimidine antifolates 1–5, MTX, PMX, LMX, LCV, or folic acid (each at 10 µM). Panel B: Data are shown for the effects of the unlabeled ligands with FRα-expressing RT16 CHO cells and FRβ-expressing D4 CHO cells. Relative binding affinities for assorted folate/antifolate substrates were determined over a range of ligand concentrations and were calculated as the inverse molar ratio of unlabeled ligands required to inhibit 3H-folic acid binding by 50%. By definition, the relative affinity of folic acid is 1. Details for the transport and binding assays are provided in the Experimental Section. Abbreviations: MTX, methotrexate; PMX, pemetrexed; LMX, lometrexol; LCV, LCV; FA, folic acid. Results are presented as mean values plus/minus SEM from 3 experiments.