Synthesis and Structure–Activity Relationships of Pteridine Dione and Trione Monocarboxylate Transporter 1 Inhibitors

[Image: see text] Novel substituted pteridine-derived inhibitors of monocarboxylate transporter 1 (MCT1), an emerging target for cancer therapy, are reported. The activity of these compounds as inhibitors of lactate transport was confirmed using a (14)C-lactate transport assay, and their potency against MCT1-expressing human tumor cells was established using MTT assays. The four most potent compounds showed substantial anticancer activity (EC(50) 37–150 nM) vs MCT1-expressing human Raji lymphoma cells.