NITROXOLINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H6N2O3
Molecular Weight	190.1555
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=CC=C(C2=C1N=CC=C2)[N+]([O-])=O

InChI

InChIKey=RJIWZDNTCBHXAL-UHFFFAOYSA-N

InChI=1S/C9H6N2O3/c12-8-4-3-7(11(13)14)6-2-1-5-10-9(6)8/h1-5,12H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25427651 | https://www.drugbank.ca/drugs/DB01422 | https://www.ncbi.nlm.nih.gov/pubmed/25074541 | https://www.ncbi.nlm.nih.gov/pubmed/27123101

Nitroxoline (8-hydroxy-5-nitroquinoline) has been used since 1962 in the treatment of urinary tract infections especially those due to gram negative bacilli (E. coli). Nitroxoline is active against most Gram-negative and –positive uropathogenic bacteria, against mycoplasmas (M. hominis, Ureaplasma urealyticum) and human pathogenic Candida spp. The mode of antibacterial and antifungal action is based on the ability of nitroxoline to chelate with various metallic bivalent cations. Nitroxoline is a fluorquinolone that is active against bacterial gyrases. This drug may also have antitumor activity by inhibition of type 2 methionine aminopeptidase (MetAP2) protein which is involved in angiogenesis. Nitroxoline induces apoptosis and inhibits glioma growth in vivo and in vitro. Due to the excellent anticancer activity and its well-known safety profile and pharmacokinetic properties, nitroxoline has been approved to enter into a phase II clinical trial in China for non-muscle invasive bladder cancer treatment

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Methionine aminopeptidase 2 4 Target ID: CHEMBL3922 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24376907	Inhibitor 8297	55.0 nM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24088053	Inhibitor 8297	1.0 µM [Ki]
Cathepsin B 9 Target ID: CHEMBL4072 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23252745 \| https://www.ncbi.nlm.nih.gov/pubmed/21598397	Inhibitor 8297	271.8 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary tract infections 205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25427651 https://www.ncbi.nlm.nih.gov/pubmed/3309832 http://en.pharmacodia.com/web/drug/1_10928.html	Primary		Approved 8429	Nibiol Approved Use Urinary antibacterial and antifungal recommended in the treatment of urinary tract infection without fever. Launch Date 1961
On-muscle invasive bladder cancer 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27123101	Primary		Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
[Is nitroxoline an allergen?].	2002 Mar-Apr	12185975
Thermodynamic investigations of nitroxoline sublimation by simultaneous DSC-FTIR method and isothermal TG analysis.	2010 Jan	19530075
Novel mechanism of cathepsin B inhibition by antibiotic nitroxoline and related compounds.	2011 Aug 1	21598397

Patents

Sample Use Guides

In Vivo Use Guide

Nitroxoline was mainly administered for treatment of uncomplicated and complicated UTI as well as for prophylaxis of recurrent UTI with daily dosages mostly between 300 and 900 mg. The treatment duration varied mainly between 3 and 10 days depending on the indication.

Route of Administration: Oral

In Vitro Use Guide

The rate of susceptibility of E. coli at a MIC of nitroxoline of ≤8 mg/l is practically 100% and has not changed over the years as shown by a recent in vitro study with 499 strains from patients with community acquired UTI showing MIC50- and MIC90-values of 2 mg/l and 4 mg/l, respectively. For other uropathogens, such as K. pneumonia, P. mirabilis. P. vulgaris, M. morganii, and S. saprophyticus the MIC50- and MIC90-values were between 4–8/ 4–8 mg/l with highest MIC of 8 mg/l.

Name

Type

Language

NITROXOLINE

Official Name

English

nitroxoline [INN]

Common Name

English

5-NITRO-8-QUINOLINOL

Systematic Name

English

NITROXOLINE [MART.]

Common Name

English

Nitroxoline [WHO-DD]

Common Name

English

NSC-74947

Code

English

NITROXOLINE [MI]

Common Name

English

A-82

Code

English

Classification Tree Code System Code

WHO-VATC

QJ01XX07