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, administered via oral gavage at dosages between 5 and 25 mg/kg, demonstrated complete dCK inhibition lasting 27 hours, with enzyme activity fully recovering after 36 hours at the 25 mg/kg dosage[1]. At dosages of 10 to 50 mg/kg, DI-87 reached plasma concentrations within 1 to 3 hours, with a plasma half-life of 4 hours[1]. Furthermore, a regimen of DI-87 at 10 mg/kg/day or 25 mg/kg twice daily, in combination with thymidine (2 g/kg; ip; twice daily), significantly reduced tumor growth in male NSG mice implanted with CEM tumors over a period of 16-18 days[1]. The study utilized 8-12 week-old male and female NSG mice with CEM tumor xenografts, finding that a 25 mg/kg dosage achieved full dCK inhibition for 27 hours with full recovery by 36 hours, while the 10 mg/kg dosage initiated recovery at 12 hours. The 5 mg/kg dosage caused minimal dCK inhibition with rapid recovery. In female NSG mice, dosages of 10, 25, or 50 mg/kg resulted in plasma concentrations lasting between 1 and 3 hours with a half-life of 4 hours, and tumor concentrations were lower than plasma levels, peaking later at 3-9 hours[1].