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
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