DI-87 is a potent, orally active deoxycytidine kinase (dCK) inhibitor with high selectivity and an EC 50 of 10.2 nM. With demonstrated antitumor efficacy, DI-87 is employed in combination therapy specifically targeting tumors that express dCK.

DCK:10.2 nM (EC50)

(S)-DI-87 exhibits a much higher IC 50 value (IC 50 =468 nM) relative to DI-87 ((R)-DI-8) (IC 50 =3.15 nM) in CEM T-ALL cells for inhibition of dCK activity[1]. DI-87 (1 μM; for 72 hours) rescues human cell line CCRF-CEM (CEM) cells from the anti-proliferative effects of gemcitabine, a dCK-dependent nucleoside analog prodrug, with an EC 50 of 10.2 nM[1].

DI-87 (5-25 mg/kg; oral gavage) exhibits full dCK inhibition for 27 hours, and enzyme activity fully recovered by 36 hours with 25 mg/kg dose[1]. DI-87 (10-50 mg/kg; oral) has plasma concentrations of between 1 and 3 hours and plasma half-life of 4 hours[1]. DI-87 (10 mg/kg/day or 25 mg/kg/twice a day; oral; for 16-18 days) with thymidine (2 g/kg; ip; twice a day) results in reduced tumor growth in male NSG mice implanted with CEM tumors[1]. Animal Model: 8-12 week-old male or female NSG mice with CEM tumor xenografts[1]Dosage: 5, 10, 25 mg/kg Administration: Oral gavage Result: The 25 mg/kg dose exhibited full dCK inhibition for 27 hours, and enzyme activity fully recovered by 36 hours. The 10 mg/kg dose resulted in full inhibition with recovery initiating at the 12 hours time point. The 5 mg/kg dose resulted in minimal dCK inhibition with rapid recovery. Animal Model: Female NSG mice with CEM tumors[1]Dosage: 10, 25, or 50 mg/kg Administration: Oral Result: Had plasma concentrations of between 1 and 3 hours and plasma half-life of 4 hours. Had tumor concentrations lower than plasma and had a later, more sustained peak at 3-9 hours.