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Details

Stereochemistry ACHIRAL
Molecular Formula C5H6BrN3O5
Molecular Weight 268.022
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Nibrozetone

SMILES

[O-][N+](=O)C1(CN(C1)C(=O)CBr)[N+]([O-])=O

InChI

InChIKey=JODKFOVZURLVTG-UHFFFAOYSA-N
InChI=1S/C5H6BrN3O5/c6-1-4(10)7-2-5(3-7,8(11)12)9(13)14/h1-3H2

HIDE SMILES / InChI

Molecular Formula C5H6BrN3O5
Molecular Weight 268.022
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

RRX-001, also known as ABDNAZ, is a dinitroazetidine derivative with potential radiosensitizing activity. Upon administration, RRx-001 is able to dilate blood vessels, thereby increasing tumor blood flow and thus improving oxygenation to the tumor site. By increasing oxygen levels, these tumor cells may be more susceptible to radiation therapy. Tumor hypoxia is correlated with tumor aggressiveness, metastasis and resistance to radiotherapy. In mouse models, RRx-001 administered intravenously as a single agent was equipotent to cisplatin while better tolerated. RRx-001 also showed activity as a radiosensitizer in both in vitro and in vivo models. The activity of RRx-001 is thought to be associated with a nucleophilic substitution by circulating thiol compounds and covalent binding of RRx-001 to cysteinyl residues in Hb, followed by the generation of nitrogen oxides. During 2014-2015 EpicentRx has launched Phase 2 trials in brain, colorectal, non-small cell lung, small cell lung and cholangiocarcinoma both alone and in combination. The anti-proliferative effects of RRx-001 are not explainable via a single mechanism. RRx-001 exerts its anti-proliferative effect, at least partially, through interference with glucose 6 phosphate dehydrogenase (G6PD), a key enzyme in the pentose phosphate pathway, responsible for maintaining adequate levels of the major cellular reductant, NADPH.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
251.1 ng/mL
83 mg/m² 1 times / week multiple, intravenous
dose: 83 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
RRX-001 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1217.5 ng × h/mL
83 mg/m² 1 times / week multiple, intravenous
dose: 83 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
RRX-001 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.45 h
83 mg/m² 1 times / week multiple, intravenous
dose: 83 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
RRX-001 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
83 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 83 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 83 mg/m2, 1 times / week
Sources: Page: p.5
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.5
Disc. AE: Infusion site pain...
AEs leading to
discontinuation/dose reduction:
Infusion site pain (50%)
Sources: Page: p.5
16.7 mg/m2 1 times / week multiple, intravenous
RP2D
Dose: 16.7 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 16.7 mg/m2, 1 times / week
Sources: Page: p.5
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.5
AEs

AEs

AESignificanceDosePopulation
Infusion site pain 50%
Disc. AE
83 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 83 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 83 mg/m2, 1 times / week
Sources: Page: p.5
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.5
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Preclinical evaluation of the metabolism and disposition of RRx-001, a novel investigative anticancer agent.
2012 Sep
Patents

Sample Use Guides

Patients with advanced cancer were assigned to receive intravenous infusions of RRx-001 at increasing doses (10 mg/m(2), 16·7 mg/m(2), 24·6 mg/m(2), 33 mg/m(2), 55 mg/m(2), and 83 mg/m(2)) either once or twice-weekly for at least 4 weeks, with at least three patients per dose cohort and allowing a 2-week observation period before dose escalation.
Route of Administration: Intravenous
RRx-001 and DHEA decreased G6PD activity in a dose dependent way. The G6PD activity for HEP-G2 decreased statiscally from control with RRx-001 and DHEA at 5, 50, and 100 uM, respectively. The G6PD activity for HT-29 decreased statiscally from control with RRx-001 at 5, 50, and 100 uM, and with DHEA at 50 and 100 uM. G6PD activity for HT-29 was statistically decreased for RRx-001 compared to DHEA at 50 and 100 uM. The G6PD activity for CACO-2 decreased statiscally from control with RRx-001 at 5, 50, and 100 uM, and with DHEA at 50 and 100 uM. G6PD activity for CaCO-2 was statistically decreased for RRx-001 compared to DHEA at 50 and 100 uM.
Substance Class Chemical
Created
by admin
on Sat Dec 16 08:33:00 GMT 2023
Edited
by admin
on Sat Dec 16 08:33:00 GMT 2023
Record UNII
7RPW6SU9SC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Nibrozetone
USAN  
Official Name English
RADIOSENSITIZER RRX-001
Common Name English
ABDNAZ
Common Name English
RRx 001 [WHO-DD]
Common Name English
NIBROZETONE [USAN]
Common Name English
2-bromo-1-(3,3-dinitroazetidin-1-yl)ethan-1-one
Systematic Name English
Ethanone, 2-bromo-1-(3,3-dinitro-1-azetidinyl)-
Systematic Name English
N-(BROMOACETYL)-3,3-DINITROAZETIDINE
Common Name English
RRx-001
Code English
Classification Tree Code System Code
EU-Orphan Drug EU/3/17/1966
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
FDA ORPHAN DRUG 577317
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
FDA ORPHAN DRUG 579817
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
FDA ORPHAN DRUG 737520
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
FDA ORPHAN DRUG 666718
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
Code System Code Type Description
CAS
925206-65-1
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
PRIMARY
FDA UNII
7RPW6SU9SC
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
PRIMARY
USAN
KL-87
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
PRIMARY
INN
12836
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
PRIMARY
SMS_ID
100000177350
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
PRIMARY
DRUG BANK
DB12060
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
PRIMARY
NCI_THESAURUS
C97130
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
PRIMARY NCIT
PUBCHEM
15950826
Created by admin on Sat Dec 16 08:33:00 GMT 2023 , Edited by admin on Sat Dec 16 08:33:00 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Reacts with thiols leading to depletion and indirect oxidative damge.
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY