In vitro and in vivo inhibition of glioblastoma and neuroblastoma with MDL101731, a novel ribonucleoside diphosphate reductase inhibitor

Cancer Res. 1996 Jan 15;56(2):359-61.


We examined the effects of MDL101731, a novel ribonucleoside reductase inhibitor, against human glioblastomas and neuroblastoma, both in vitro and in xenograft models, to determine its activity against malignant brain tumors. MDL101731 produced a concentration-dependent inhibition of both glioblastoma cell lines (HS683 and J889H) and neuroblastoma (SK-N-MC) in nanomolar concentrations (IC50, 30-90 nM). s.c. xenografts of human glioblastoma (D54) in athymic mice increased to five times their initial volume at a median of 7.4 days in control animals, while tumor regression occurred in 12 of 12 animals treated with MDL101731 (100 mg/kg, i.p., two times/week) during 22 days of treatment (P < 0.0001). Intracerebral implants of D54 carried a median survival of 20 days in control animals, whereas animals receiving MDL101731 (100 mg/kg, i.p., two times/week, days 10-35) had a median survival of 46.5 days (P < 0.0001). Intracerebral xenografts of SK-N-MC in athymic mice resulted in a median survival of 23 days in control animals and 26 days in animals treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea 20 mg/kg/week, i.v. x 2; difference not significant). There was 90% survival in animals treated with MDL101731 (200 mg/kg, i.v., two times/week, days 7-35) up to 90 days after implant. These studies indicate that MDL101731 has potent antiproliferative activity against human malignant brain tumors.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / enzymology
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Enzyme Inhibitors / pharmacology*
  • Glioblastoma / drug therapy*
  • Glioblastoma / enzymology
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Ribonucleoside Diphosphate Reductase / antagonists & inhibitors*
  • Transplantation, Heterologous


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Deoxycytidine
  • Ribonucleoside Diphosphate Reductase
  • tezacitabine