Author: Jamieson, Stephen M. F. ; Wilson, William R. ; Wang, Jingli ; Hicks, Kevin O. ; Bonnet, Muriel ; Wong, Way Wua ; Anderson, Robert F. ; Qi, Wen ; Stevenson, Ralph J. ; Shome, Avik ; Hong, Cho Rong ; Liew, Lydia P. ; Pruijn, Frederik B. ; Hay, Michael P. ; Gu, Yongchuan

Innovations in the field of radiotherapy such as stereotactic body radiotherapy, along with the advent of radio-immuno-oncology, herald new opportunities for classical oxygen-mimetic radiosensitizers. The role of hypoxic tumor cells in resistance to radiotherapy and in suppression of immune response continues to endorse tumor hypoxia as a bona fide, yet largely untapped, drug target. Only nimorazole is used clinically as a radiosensitizer, and there is a dearth of new radiosensitizers in development. Here we present a survey of novel nitroimidazole alkylsulfonamides and document their cytotoxicity and ability to radiosensitize anoxic tumor cells in vitro. We use a phosphate prodrug approach to increase aqueous solubility and to improve tumor drug delivery. A 2-nitroimidazole and a 5-nitroimidazole analogue demonstrated marked tumor radiosensitization in either ex vivo assays of surviving clonogens or tumor regrowth delay.

01 Dec 2013·BMC CancerQ2 · MEDICINE

The prospective application of a hypoxic radiosensitizer, doranidazole to rat intracranial glioblastoma with blood brain barrier disruption

Q2 · MEDICINE

ArticleOA

Author: Hironobu Yasui ; Mikinori Kuwabara ; Masaki Nagane ; Taketoshi Asanuma ; Osamu Inanami ; Junichi Kino ; Shunsuke Meike ; Tohru Yamamori ; Nobuo Kubota

AbstractBackgroundGlioblastoma is one of the intractable cancers and is highly resistant to ionizing radiation. This radioresistance is partly due to the presence of a hypoxic region which is widely found in advanced malignant gliomas. In the present study, we evaluated the effectiveness of the hypoxic cell sensitizer doranidazole (PR-350) using the C6 rat glioblastoma model, focusing on the status of blood brain barrier (BBB).MethodsReproductive cell death in the rat C6 glioma cell line was determined by means of clonogenic assay. An intracranial C6 glioma model was established for the in vivo experiments. To investigate the status of the BBB in C6 glioma bearing brain, we performed the Evans blue extravasation test. Autoradiography with [14C]-doranidazole was performed to examine the distribution of doranidazole in the glioma tumor. T2-weighted MRI was employed to examine the effects of X-irradiation and/or doranidazole on tumor growth.ResultsDoranidazole significantly enhanced radiation-induced reproductive cell death in vitro under hypoxia, but not under normoxia. The BBB in C6-bearing brain was completely disrupted and [14C]-doranidazole specifically penetrated the tumor regions. Combined treatment with X-irradiation and doranidazole significantly inhibited the growth of C6 gliomas.ConclusionsOur results revealed that BBB disruption in glioma enables BBB-impermeable radiosensitizers to penetrate and distribute in the target region. This study is the first to propose that in malignant glioma the administration of hydrophilic hypoxic radiosensitizers could be a potent strategy for improving the clinical outcome of radiotherapy without side effects.

01 Jun 2008·Radiotherapy and OncologyQ2 · MEDICINE

Efficacy of novel hypoxic cell sensitiser doranidazole in the treatment of locally advanced pancreatic cancer: Long-term results of a placebo-controlled randomised study

Q2 · MEDICINE

Article

Author: Yuta Shibamoto ; Atsutake Okamoto ; Seiki Matsuno ; Makoto Sunamura ; Katsuyuki Karasawa ; Kenji Nemoto ; Yasumasa Nishimura

Novel hypoxic cell radiosensitiser doranidazole was tested for unresectable pancreatic cancer administered at intraoperative radiotherapy. Short-term survival was not different. However, difference has been observed concerning 3-year survival (doranidazole group vs. placebo; 23% vs. 0%, p=0.0192). This sensitiser might be effective in improving long-term survival for pancreatic cancer.

100 Deals associated with Doranidazole

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KEGG	Wiki	ATC	Drug Bank
D01834	-	-	-

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Indication	Highest Phase	Country/Location	Organization	Date
Esophageal Carcinoma	NDA/BLA	-	Pola Chemical Industries, Inc.	-
Lung Cancer	NDA/BLA	-	Pola Chemical Industries, Inc.	-
Non-Small Cell Lung Cancer	NDA/BLA	Japan	Pola Pharma, Inc.	-
Pancreatic Cancer	NDA/BLA	Japan	Pola Pharma, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2006	Phase 1/2	Non-Small Cell Lung Cancer	37	PR-350	(bdbfplxmbf) = rhhsmdtldg yfsctigvdz (hainkjncmj ) View more	-	20 Jun 2006

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