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Synthesis and structure-activity relationships of pteridine dione and trione monocarboxylate transporter 1 inhibitors.

ABSTRACT: 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 (EC50 37-150 nM) vs MCT1-expressing human Raji lymphoma cells.

SUBMITTER: Wang H

PROVIDER: S-EPMC4161152 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Synthesis and structure-activity relationships of pteridine dione and trione monocarboxylate transporter 1 inhibitors.

Wang Hui H Yang Chunying C Doherty Joanne R JR Roush William R WR Cleveland John L JL Bannister Thomas D TD

Journal of medicinal chemistry 20140822 17

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 (EC50 37-150 nM) vs MCT1-expressing human Raji lymphoma cells. ...[more]

PMID: 25068893

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