DORANIDAZOLE

Details

Stereochemistry	RACEMIC
Molecular Formula	C8H13N3O6
Molecular Weight	247.2053
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC[C@@H](O)[C@H](CO)OCN1C=CN=C1[N+]([O-])=O

InChI

InChIKey=FIITXXIVUIXYMI-RQJHMYQMSA-N

InChI=1S/C8H13N3O6/c12-3-6(14)7(4-13)17-5-10-2-1-9-8(10)11(15)16/h1-2,6-7,12-14H,3-5H2/t6-,7+/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/23496909
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/12056332 and http://www.ncbi.nlm.nih.gov/pubmed/7642409

PR-69 (Doranidazole) is a hypoxic radiosensitizer, and is a derivative of 2-nitroimidazole intended to reduce neurotoxicity due to its blood brain barrier (BBB) impermeability. Several studies have shown that doranidazole has a radiosensitizing effect under hypoxia, both in vitro and in vivo. Based on these studies, a phase III trial of doranidazole against advanced pancreatic cancer was performed; it was demonstrated that treatment with doranidazole following radiation significantly improved the tumor mass reduction rate and extended patient survival. Various results have suggested that doranidazole has promising potential for hypoxia-targeting chemoradiotherapy.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Apoptosis 155 Target ID: map04210 Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=12056329	Modulator 828
Dihydropyrimidine dehydrogenase [NADP(+)] 4 Target ID: O89000 Gene ID: 81656.0 Gene Symbol: Dpyd Target Organism: Rattus norvegicus (Rat) Sources: http://www.ncbi.nlm.nih.gov/pubmed/11320669	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pancreatic cancer 97 Sources: http://www.ncbi.nlm.nih.gov/pubmed/15084982	Primary		Phase III 656	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: http://www.ncbi.nlm.nih.gov/pubmed/17512126	Primary		Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Phase III trial of radiosensitizer PR-350 combined with intraoperative radiotherapy for the treatment of locally advanced pancreatic cancer.	2004 Apr	15084982
Phase I/II trial of sequential chemoradiotherapy using a novel hypoxic cell radiosensitizer, doranidazole (PR-350), in patients with locally advanced non-small-cell lung Cancer (WJTOG-0002).	2007 Nov 1	17512126
The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation.	2007 Oct 6	17919337
The prospective application of a hypoxic radiosensitizer, doranidazole to rat intracranial glioblastoma with blood brain barrier disruption.	2013 Mar 8	23496909

Patents

Sample Use Guides

In Vivo Use Guide

Mice: The radiation-induced growth delay of SCCVII tumors was significantly enhanced and the TCD(50/120) was reduced by a factor of 1.33 when 200 mg/kg PR-69 (Doranidazole) was injected, i.v., 20 min prior to tumor irradiation.

Route of Administration: Intravenous

In Vitro Use Guide

With the addition of 5 mmol/L doranidazole (PR-69), the cell killing by 30 Gy irradiation under hypoxic conditions was significantly increased from 22.2% to 36.4% in five colorectal cancer cell lines: VoLo, HT-29, DLD-1, Colo 201, SW 620.

Name

Type

Language

DORANIDAZOLE

Official Name

English

1,2,4-BUTANETRIOL, 3-((2-NITRO-1H-IMIDAZOL-1-YL)METHOXY)-, (2R,3S)-REL-

Systematic Name

English

PR-350

Code

English

RP-343

Code

English

doranidazole [INN]

Common Name

English

(2RS,3SR)-3-((2-NITROIMIDAZOL-1-YL)METHOXY)BUTANE-1,2,4-TRIOL

Systematic Name

English

DORANIDAZOLE [JAN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

665218