DI-87 (TRE-515) is a novel and orally available dCK (deoxycytidine kinase) inhibitor with good in vitro activity and low protein binding. DI-87 binds to dCK and prevents the phosphorylation of deoxycytidine by dCK, which reduces the production of dNTP and cell cycle arrest (especially in S phase). When combined with thymidine, DI-87 significantly inhibits tumor growth.

DCK:10.2 nM (EC50)

Methods: CEM cells were seeded at 1 × 10 3 cells/well in white opaque 384-well plates at 50 μl/well and treated as indicated. After incubation with increasing concentrations (2 nM-10 μM) of gemcitabine and 1 μM DI-87 for 72 h, 50 μl of CellTiter-Glo reagent (diluted 1:5 in dH2O) was added to each well, the plates were incubated at room temperature for 5 m, and luminescence was measured using a BioTek microplate luminometer.
Results: The cytotoxic effect of gemcitabine requires dCK, and administration of DI-87 completely blocked cytotoxicity after gemcitabine treatment, demonstrating dCK inhibition by DI-87. [1]

Methods: Female NSG mice bearing CEM tumors were treated with DI-87 (10, 25, or 50 mg/kg, orally) and DI-87 plasma and tumor concentrations were assessed.
Results: Plasma DI-87 concentrations peaked between 1 and 3 hours; tumor concentrations were lower than plasma and had a later, more sustained peak at 3-9 hours. [1]