Disease relevance of Doranidazole

• A great advantage of RP-343 over RP-170 and etanidazole is its very much lower toxicity; their LD50 in mice were > 6.0, 4.3 and 4.8 g/kg, respectively, on i.v. injection [1].
• However, few data have been reported on the radiosensitivity and hypoxic fraction of human pancreatic cancers, and the efficacy of doranidazole against them [2].
• The proportions of the cells at the sub-G1 peak in a flow cytometric measurement was not very different among the irradiations at 5 Gy under the aerobic condition, 15 Gy under hypoxia, and 10 Gy with 1 mM doranidazole under hypoxia [3].
• Effect of a hypoxic cell sensitizer doranidazole on the radiation-induced apoptosis of mouse L5178Y lymphoma cells [3].

High impact information on Doranidazole

• Doranidazole had definite in vitro and in vivo effects on all pancreatic cancer cell lines [2].
• These cells were treated with 0.4 or 1 mM doranidazole for 45 mm prior to and during aerobic or hypoxic irradiation, and the cell survival was determined using the colony assay [2].
• On the other hand, 200 mg/kg of doranidazole exerted no influence on the radiation-induced growth delay in MIA PaCa-2 xenografts [4].
• Effects of hypoxic cell radiosensitizer doranidazole (PR-350) on the radioresponse of murine and human tumor cells in vitro and in vivo [4].
• This study was performed to confirm the radiation-chemical properties of the 2-nitroimidazole derivative doranidazole, (+/-)-(2RS,3SR)-3-[(2-nitroimdazol-1-yl)-methoxy]butane-1,2,4-triol [CAS 137339-64-1], PR-350, which was synthesized as a hypoxic cell radiosensitizer with low toxicity [5].

Chemical compound and disease context of Doranidazole

• BACKGROUND AND PURPOSE: A clinical study of the new 2-nitroimidazole nucleoside analogue doranidazole (PR-350) in combination with intraoperative radiotherapy is ongoing in Japan for localized unresectable pancreatic cancer [2].

Biological context of Doranidazole

• A phase Ia study of a 2-nitroimidazole nucleoside analog radiosensitizer doranidazole was conducted to evaluate its toxicity and pharmacokinetics in patients undergoing conventional external beam radiotherapy [6].
• In the assay of DNA ladder formation, DNA fragmentation was observed following irradiation under an aerobic or hypoxic condition with or without doranidazole [3].

Associations of Doranidazole with other chemical compounds

• We investigated the sensitizing effect of the 2-nitroimidazole analogue doranidazole, a new hypoxic radiosensitizer, on radiation-induced apoptosis in L5178Y cells [3].

Gene context of Doranidazole

• In vivo efficacy and pharmacokinetics of a new hypoxic cell radiosensitizer doranidazole in SUIT-2 human pancreatic cancer xenografted in mouse pancreas [7].

Analytical, diagnostic and therapeutic context of Doranidazole

• In vivo, Balb/c nude mice bearing the pancreatic cancers (about 200 mg) on their backs received whole-body irradiation either after cervical dislocation, without physical restraint or anesthesia, or 20 min after intravenous injection of 100 mg/kg (0.4 mmol/kg) or 250 mg/kg (1 mmol/kg) of doranidazole [2].
• The radiation-induced growth delay of CFPAC-1 xenografts in nude mice was significantly enhanced and the TCD(50/90) was reduced by a factor of 1.30 by 200 mg/kg doranidazole [4].

References