This orally bioavailable MCT1 inhibitor (FW = 515.51 g/mol; CASs = 733809-45-5 and 1448671-31-5), also named (S)-5-(4-hydroxy-4- methylisoxazolidine-2-carbonyl)-1-isopropyl-3-methyl-6-((3-methyl-5-(tri fluoromethyl)-1H-pyrazol-4-yl)methyl)-thieno[2,3-d]pyrimidine-2,4(1H, 3H) -dione, selectively targets the Monocarboxylate Transporter-1 (IC50 = 1.6 nM) and is ~6x less active toward MCT2. AZD3965 does not inhibit MCT4, even at 10 μM. MCT1 and MCT4 are primarily involved in lactate transport, targeting highly glycolytic cancer cells, especially those that are hypoxic. The latter property suggests that the combined use with a vascular-disrupting anticancer agent (such as combrestatin) may improve the inhibitory action of AZD-3965 against cancer cells.
