Identification
- Generic Name
- Cinoxacin
- DrugBank Accession Number
- DB00827
- Background
Synthetic antimicrobial related to oxolinic acid and nalidixic acid and used in urinary tract infections.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
Structure for Cinoxacin (DB00827)
- Weight
- Average: 262.2182
Monoisotopic: 262.05897144 - Chemical Formula
- C12H10N2O5
- Synonyms
- 1-ethyl-6,7-methylenedioxy-4(1H)-oxocinnoline-3-carboxylic acid
- 5-Ethyl-8-oxo-5,8-dihydro-1,3-dioxa-5,6-diaza-cyclopenta[b]naphthalene-7-carboxylic acid
- Cinoxacin
- Cinoxacine
- Cinoxacino
- Cinoxacinum
- External IDs
- 64716
Pharmacology
- Indication
For the treatment of initial and recurrent urinary tract infections in adults caused by the following susceptible microorganisms: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K. pneumoniae), and Enterobacter species.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Cinoxacin is a synthetic antibacterial agent with in vitro activity against many gram-negative aerobic bacteria, particularly strains of the Enterobacteriaceae family. Cinoxacin inhibits bacterial deoxyribonucleic acid (DNA) synthesis, is bactericidal, and is active over the entire urinary pH range. Cross resistance with nalidixic acid has been demonstrated.
- Mechanism of action
Evidence exists that cinoxacin binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis. It appears to also inhibit DNA gyrase. This enzyme is necessary for proper replicated DNA separation. By inhibiting this enzyme, DNA replication and cell division is inhibited.
Target Actions Organism ADNA gyrase subunit A inhibitorHaemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) UDNA intercalationHumans - Absorption
Rapidly absorbed after oral administration. While concurrent food intake may delay the drug absorption, the total drug absorption is not affected.
- Volume of distribution
Not Available
- Protein binding
60 to 80%
- Metabolism
Hepatic, with approximately 30-40% metabolized to inactive metabolites.
- Route of elimination
Not Available
- Half-life
While the mean serum half-life is 1.5 hours, the half-life may exceed 10 hours in case of renal impairment.
- Clearance
Not Available
- Adverse Effects
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Oral, subcutaneous, and intravenous LD50 in the rat is 3610 mg/kg, 1380 mg/kg, and 860 mg/kg, respectively. Oral, subcutaneous, and intravenous LD50 in the mouse is 2330 mg/kg, 900 mg/kg, and 850 mg/kg, respectively. Symptoms following an overdose of cinoxacin may include gastrointestinal effects such as anorexia, nausea, vomiting, epigastric distress, and diarrhea; the severity of the epigastric distress and diarrhea are dose-related. Headache, dizziness, insomnia, photophobia, tinnitus, and a tingling sensation have also been reported in some patients.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcarbose The therapeutic efficacy of Acarbose can be increased when used in combination with Cinoxacin. Aceclofenac Aceclofenac may increase the neuroexcitatory activities of Cinoxacin. Acemetacin Acemetacin may increase the neuroexcitatory activities of Cinoxacin. Acenocoumarol The therapeutic efficacy of Acenocoumarol can be increased when used in combination with Cinoxacin. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Cinoxacin. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Cinobac (Oclassen) / Mecicon (Chung Mei) / Tatsulexin (Tatsumi Kagaku) / Urocinox (BioHealth Pharmaceuticals)
Categories
- ATC Codes
- J01MB06 — Cinoxacin
- Drug Categories
- Anti-Bacterial Agents
- Anti-Infective Agents
- Antibacterials for Systemic Use
- Antiinfectives for Systemic Use
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Enzyme Inhibitors
- Fluoroquinolones
- Heterocyclic Compounds, Fused-Ring
- Moderate Risk QTc-Prolonging Agents
- OAT1/SLC22A6 inhibitors
- QTc Prolonging Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cinnolines. These are organic aromatic compounds containing a benzene fused to a pyridazine ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazanaphthalenes
- Sub Class
- Benzodiazines
- Direct Parent
- Cinnolines
- Alternative Parents
- Benzodioxoles / Pyridazines and derivatives / Benzenoids / Vinylogous amides / Heteroaromatic compounds / Oxacyclic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Acetals show 4 more
- Substituents
- Acetal / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzodioxole / Carboxylic acid / Carboxylic acid derivative / Cinnoline / Heteroaromatic compound / Hydrocarbon derivative show 10 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- oxacycle, oxo carboxylic acid, cinnolines (CHEBI:3716)
- Affected organisms
- Enteric bacteria and other eubacteria
Chemical Identifiers
- UNII
- LMK22VUH23
- CAS number
- 28657-80-9
- InChI Key
- VDUWPHTZYNWKRN-UHFFFAOYSA-N
- InChI
- InChI=1S/C12H10N2O5/c1-2-14-7-4-9-8(18-5-19-9)3-6(7)11(15)10(13-14)12(16)17/h3-4H,2,5H2,1H3,(H,16,17)
- IUPAC Name
- 1-ethyl-4-oxo-1H,4H,7H-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid
- SMILES
- CCN1N=C(C(O)=O)C(=O)C2=CC3=C(OCO3)C=C12
References
- Synthesis Reference
White, W.A.; U.S. Patent 3,669,965; June 13, 1972; assigned to Eli Lilly & Company.
US3669965- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014965
- KEGG Drug
- D00872
- KEGG Compound
- C08052
- PubChem Compound
- 2762
- PubChem Substance
- 46507547
- ChemSpider
- 2660
- BindingDB
- 39350
- 2550
- ChEBI
- 3716
- ChEMBL
- CHEMBL1208
- ZINC
- ZINC000000032350
- Therapeutic Targets Database
- DAP000999
- PharmGKB
- PA449007
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Cinoxacin
- FDA label
- Download (37.2 KB)
- MSDS
- Download (53.7 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 0 Terminated Treatment Osteomyelitis 1
Pharmacoeconomics
- Manufacturers
- Eli lilly and co
- Teva pharmaceuticals usa inc
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Capsule 500 MG - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 261-262 White, W.A.; U.S. Patent 3,669,965; June 13, 1972; assigned to Eli Lilly & Company. logP 1.5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.961 mg/mL ALOGPS logP 1.25 ALOGPS logP 1.72 Chemaxon logS -2.4 ALOGPS pKa (Strongest Acidic) 4.93 Chemaxon pKa (Strongest Basic) -4.7 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 88.43 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 73.6 m3·mol-1 Chemaxon Polarizability 24.72 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9902 Blood Brain Barrier + 0.7001 Caco-2 permeable - 0.515 P-glycoprotein substrate Non-substrate 0.5087 P-glycoprotein inhibitor I Non-inhibitor 0.8358 P-glycoprotein inhibitor II Non-inhibitor 0.8382 Renal organic cation transporter Non-inhibitor 0.7213 CYP450 2C9 substrate Non-substrate 0.8137 CYP450 2D6 substrate Non-substrate 0.8119 CYP450 3A4 substrate Non-substrate 0.5503 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6 Ames test AMES toxic 0.9106 Carcinogenicity Non-carcinogens 0.8656 Biodegradation Not ready biodegradable 0.8917 Rat acute toxicity 1.8922 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8812 hERG inhibition (predictor II) Non-inhibitor 0.9074
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 167.1510199 predictedDarkChem Lite v0.1.0 [M-H]- 167.2634199 predictedDarkChem Lite v0.1.0 [M-H]- 155.23686 predictedDeepCCS 1.0 (2019) [M+H]+ 167.7589199 predictedDarkChem Lite v0.1.0 [M+H]+ 167.3823199 predictedDarkChem Lite v0.1.0 [M+H]+ 157.59486 predictedDeepCCS 1.0 (2019) [M+Na]+ 167.3705199 predictedDarkChem Lite v0.1.0 [M+Na]+ 163.688 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Dna topoisomerase type ii (atp-hydrolyzing) activity
- Specific Function
- DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, inc...
- Gene Name
- gyrA
- Uniprot ID
- P43700
- Uniprot Name
- DNA gyrase subunit A
- Molecular Weight
- 97817.145 Da
References
- Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. [Article]
- Drlica K, Zhao X: DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev. 1997 Sep;61(3):377-92. [Article]
- Neugebauer U, Szeghalmi A, Schmitt M, Kiefer W, Popp J, Holzgrabe U: Vibrational spectroscopic characterization of fluoroquinolones. Spectrochim Acta A Mol Biomol Spectrosc. 2005 May;61(7):1505-17. [Article]
- Tuma J, Connors WH, Stitelman DH, Richert C: On the effect of covalently appended quinolones on termini of DNA duplexes. J Am Chem Soc. 2002 Apr 24;124(16):4236-46. [Article]
Unknown
Intercalation
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Tuma J, Connors WH, Stitelman DH, Richert C: On the effect of covalently appended quinolones on termini of DNA duplexes. J Am Chem Soc. 2002 Apr 24;124(16):4236-46. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- This drug is a fluoroquinolone, and these agents are known to inhibit CYP1A2.
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Zhang L, Wei MJ, Zhao CY, Qi HM: Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes. Acta Pharmacol Sin. 2008 Dec;29(12):1507-14. doi: 10.1111/j.1745-7254.2008.00908.x. [Article]
- Shahzadi A, Javed I, Aslam B, Muhammad F, Asi MR, Ashraf MY, Zia-ur-Rahman: Therapeutic effects of ciprofloxacin on the pharmacokinetics of carbamazepine in healthy adult male volunteers. Pak J Pharm Sci. 2011 Jan;24(1):63-8. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:45