title: 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.
authors: Department of Chemistry, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
authors: Hui
authors: H
authors: Wang
authors: Chunying
authors: C
authors: Yang
authors: Joanne R
authors: JR
authors: Doherty
authors: William R
authors: WR
authors: Roush
authors: John L
authors: JL
authors: Cleveland
authors: Thomas D
authors: TD
authors: Bannister
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011621:Pteridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000970:Antineoplastic Agents; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D011621:Pteridines; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1