AZD3965 is a first-in-class, cell permeable high affinity ligand of monocarboxylate transporter 1 (MCT1), binding to the protein with a Ki value of 1.6 nM, with 6 fold selectivity over the closely related MCT2, and does not bind to MCT4 at a concentration of 10 μM. AZD3965 offers a novel mechanism for targeting the metabolic phenotype in tumors that preferentially express MCT1 such as lymphoma cancer cell lines, in which both lactate transport and cell growth are potently inhibited by AZD3965, and a strong cytotoxic effect is also induced by AZD3965 for other cell lines that are preferentially express MCT1. Blocking lactate transport in vitro also leads to a rapid inhibition of glucose uptake in the RajiBurkitt's lymphoma cell line. In vitro combination studies show that the cell death can be enhanced by Doxorubicin through lactate transport inhibition in which AZD3965 experts the effort. In vivo, AZD3965 is well tolerated and induces a dose and time dependent accumulation of lactate in the tumors, suppressing tumor growth in the Raji model, potentiating the effects of Rituxan, Doxorubicin (Axon 4072) and Bendamustine.

Keywords: AZD3965 | Supplier | MCT1 inhibitor | AZD-3965 | AZD 3965 | CT-A3965 | CAS [1448671-31-5] | Monocarboxylates | MCT | Inhibitor | Proteins