Disease relevance of Doranidazole

• Optical isomers of a new 2-nitroimidazole nucleoside analog (PR-350 series): radiosensitization efficiency and toxicity [1].
• In five of seven pancreatic cancer cell lines in which the number of dead cells was determined 5 days after 30 Gy irradiation in the presence of PR-350, the number was significantly increased under hypoxic conditions, but not under aerobic conditions [2].
• In vivo study of radiosensitizing effect of hypoxic cell radiosensitizer PR-350 on a human small cell lung cancer [3].
• The results indicate that PR-350 can enhance the killing of pancreatic cancer cells by high-dose irradiation under hypoxia, which supports its clinical radiosensitizing effects when administered during intraoperative irradiation to pancreatic cancer [2].

High impact information on Doranidazole

• The concentration of PR-28 in the murine sciatic nerve was lower than that of PR-350 [1].
• The LD50 in mice were 5.8 g/kg for PR-350, approximately 7 g/kg for PR-28, 4 g/kg for PR-68, and 6 g/kg for PR-44 and PR-69 [1].
• Effects of PR-350, a newly developed radiosensitizer, on dihydropyrimidine dehydrogenase activity and 5-fluorouracil pharmacokinetics [4].
• These results suggest that the effect of PR-350 on 5-FU pharmacokinetics is much less than that of BVU and that the enhancement of 5-FU toxicity by PR-350 is less than we initially anticipated [4].
• The radiosensitizing effects of PR-350, a nitroimidazole derivative, were examined concerning the cell killing of human pancreatic cancer cell lines exposed to high doses of gamma-ray irradiation in vitro [2].

Anatomical context of Doranidazole

• In an ex vivo study, DPD activities in hepatic cytosols obtained from animals which had received PR-350 over 4 days (200 mg/kg per day) were not significantly different from those in animals which had not [4].

Associations of Doranidazole with other chemical compounds

• Phase Ia study of a hypoxic cell sensitizer doranidazole (PR-350) in combination with conventional radiotherapy [5].
• One hundred mice were used to evaluate the effect of PR-350 on tumor volume after irradiation, and the other mice were used for histological study: hematoxylin and eosin staining, immunohistochemistry (Ki-67 and p53), TUNEL staining, and electromicroscopy [3].

Gene context of Doranidazole

• In an in vitro study with hepatic cytosol, DPD activity was dose-dependently reduced by PR-350 at 0.5, 1.0, and 2.0 mmol/l to 75.5%, 64.9%, and 61.5%, respectively, of the control values [4].

Analytical, diagnostic and therapeutic context of Doranidazole

• We examined the effect of PR-350 on the changes of tumor volume and microscopic features following irradiation [3].
• The selective radiosensitive effect of PR-350 on hypoxic cells was also confirmed by flow cytometry [2].
• Any differences between the PR-350 group (n = 22) and control group (n = 25) were not statically significant [6].
• RESULTS: The intratumoral concentration of PR-350 reached the maximum value of 77.7 mg/kg 20 min after intravenous injection [7].

References