AZD3965

Background Information:

AZD3965 is a first-in-class, clinical stage, 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 (Our product No: CT-DOXO) 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 and Bendamustine.

Reference:

1. R. Pola?ski , et al, Activity of the monocarboxylate transporter 1
inhibitor AZD3965 in small cell lung cancer, Clin Cancer Res. 2014 Feb
15; 20(4):926-37. doi: 10.1158/1078-0432.CCR-13-2270. Epub 2013 Nov 25.
PubMed PMID: 24277449; PubMed Central PMCID: PMC3929348.
2. B. M. Bola, et al, Inhibition of Monocarboxylate Transporter-1 (MCT1)
by AZD3965 Enhances Radiosensitivity by Reducing Lactate Transport,Mol
Cancer Ther, 2014, 13(12); 2805–16.

APIM050313: AZD3965

CAS No.: 1448671-31-5.
Molecular Formula: C₂₁H₂₄F₃N₅O₅S.
Molecular Weight: 515.5.
Purity: >99% (HPLC at 214 and 254 nm), >98.5% Optical Purity (Chiral HPLC).
QC: HPLC-MS, ¹HNMR, Chiral HPLC, and Quantitative Elemental Analysis.
Solubility: Soluble in DMSO.
Storage: Store at 0°C (short term), -20°C (long term), desiccated.