COR-L103 tumor-bearing mice receive 100 mg/kg AZD3965 or a vehicle BID for 21 days, with tumor volume tracked. Pharmacokinetic analysis reveals that 100 mg/kg AZD3965 BID achieves free AZD3965 concentrations predicted to block lactate transport. The treatment with AZD3965 significantly curtails COR-L103 tumor growth; however, tumor regression is not observed, aligning with the understanding that AZD3965 primarily targets the tumor's hypoxic fraction^[2].

AZD3965 is engineered to selectively block Monocarboxylate Transporter-1 (MCT1), thus anticipated to affect lactate transport into and out of cells^[1].

AZD3965 treatment leads to a 3.7-fold rise in intracellular lactate levels under hypoxic conditions in COR-L103 cells, and increases of 3.7-fold and 3.9-fold in NCI-H1048 cells under normoxic and hypoxic conditions, respectively. In all other scenarios, a less than 1.9-fold increase is observed. These results align with AZD3965's mechanism of blocking lactate transport in cells, reducing cell numbers, and indicate its action through MCT1 inhibition. Furthermore, overexpression of MCT1 in NCI-H1048 cells elevates the EC50 from 0.14 nM to 10.5 nM, supporting the action of AZD3965 via MCT1 inhibition^[2].