Inhibitor of Monocarboxylate transporter 1;Inhibitor of Monocarboxylate transporter 2
Product Description
Information
AZD3965 AZD3965 is a potent, selective and orally available monocarboxylate transporter 1 ( MCT1 ) inhibitor with a binding affinity of 1.6 nM, 6-fold selective over MCT2. Phase 1.
Targets
MCT1
In vitro
In lymphoma cell lines that preferentially express MCT1, AZD3965 potently inhibits lactate transport and cell growth. AZD3965 inhibits MCT1 activity in cells, and shows higher sensitivity in hypoxia. In H526, HGC27 cells and DMS114 cells, AZD3965 increases intracellular lactate and significantly reduces lactate uptake.
In vivo
In nonobese diabetic scid-γ mice bearing COR-L103 xenografts, AZD3965 (100 mg/kg, p.o.) reduces tumor growth and increased intratumor lactate. In mice bearing H526 tumors, AZD3965 (100 mg/kg, p.o.) causes increased lactate concentration, a reduction in growth and increased radiation sensitivity.
1.Polański R, Hodgkinson CL, Fusi A, Nonaka D, Priest L, Kelly P, Trapani F, Bishop PW, White A, Critchlow SE et al.. (2014) Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer.. Clin Cancer Res, 20 (4):(926-937). [PMID:24277449]
2.Noble RA, Bell N, Blair H, Sikka A, Thomas H, Phillips N, Nakjang S, Miwa S, Crossland R, Rand V et al.. (2017) Inhibition of monocarboxyate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and Burkitt lymphoma.. Haematologica, 102 (7):(1247-1257). [PMID:28385782]
3.Curtis NJ, Mooney L, Hopcroft L, Michopoulos F, Whalley N, Zhong H, Murray C, Logie A, Revill M, Byth KF et al.. (2017) Pre-clinical pharmacology of AZD3965, a selective inhibitor of MCT1: DLBCL, NHL and Burkitt's lymphoma anti-tumor activity.. Oncotarget, 8 (41):(69219-69236). [PMID:29050199]
F23081071