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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyPyrazinamide
Targets (1)
Enzymes (4)
Identification
- Name
- Pyrazinamide
- Accession Number
- DB00339 (APRD01206)
- Type
- Small Molecule
- Groups
- Approved
- Description
A pyrazine that is used therapeutically as an antitubercular agent.
- Structure
Structure for DB00339 (Pyrazinamide)
- Synonyms
- 2-carbamylpyrazine
- 2-pyrazinecarboxamide
- Aldinamide
- Pirazinamida
- Pirazinamide
- Pyrazinamid
- Pyrazinamida
- Pyrazinamide
- Pyrazinamidum
- Pyrazine carboxamide
- pyrazine-2-carboxamide
- Pyrazineamide
- Pyrazinecarboxamide
- Pyrazinoic acid amide
- Pyrizinamide
- External IDs
- D-50 / MK-56 / NSC-14911 / PZA / Z
- Product Ingredients
- Not Available
- Approved Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Pdp-pyrazinamide Tablet 500 mg Oral Pendopharm Division Of De Pharmascience Inc 1984-12-31 Not applicable Canada 
Tebrazid Tab 500mg Tablet 500 mg Oral Valeant Canada Lp Valeant Canada S.E.C. 1973-12-31 Not applicable Canada - Approved Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Pyrazinamide Tablet 500 mg/1 Oral Remedy Repack 2013-08-21 2017-01-13 US 
Pyrazinamide Tablet 500 mg/1 Oral A S Medication Solutions 1995-04-01 2017-06-20 US Pyrazinamide Tablet 500 mg/1 Oral A S Medication Solutions 1971-06-03 2017-06-20 US Pyrazinamide Tablet 500 mg/1 Oral Mikart, Inc. 1992-06-30 2017-01-11 US Pyrazinamide Tablet 500 mg/1 Oral Clinical Solutions Wholsesale 1971-06-03 2017-06-20 US Pyrazinamide Tablet 500 mg/1 Oral DAVA Pharmaceuticals, Inc. 1971-06-03 Not applicable US Pyrazinamide Tablet 500 mg/1 Oral Remedy Repack 2008-05-21 Not applicable US Pyrazinamide Tablet 500 mg/1 Oral Remedy Repack 2011-06-30 2016-10-21 US Pyrazinamide Tablet 500 mg/1 Oral A S Medication Solutions 1995-04-01 2017-06-20 US Pyrazinamide Tablet 500 mg/1 Oral Amerincan Health Packaging 2015-09-01 Not applicable US Pyrazinamide Tablet 500 mg/1 Oral Department Of State Health Services, Pharmacy Branch 1995-04-01 Not applicable US Pyrazinamide Tablet 500 mg/1 Oral Remedy Repack 2016-12-27 Not applicable US Pyrazinamide Tablet 500 mg/1 Oral Remedy Repack 2013-02-26 2016-10-13 US Pyrazinamide Tablet 500 mg/1 Oral Versa Pharm Incorporated 1995-04-01 Not applicable US - Approved Over the Counter Products
- Not Available
- Unapproved/Other Products
- Not Available
- International/Other Brands
- Piraldina (Bracco) / Prazina (Armoxindo) / Pyrafat (Riemser) / Pyrazide (Sanofi-Aventis) / Tebrazid (Valeant) / Tisamid (Orion)
- Brand mixtures
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Rifater Tablet, sugar coated Oral Remedy Repack 2010-09-15 2016-10-13 US - Categories
- UNII
- 2KNI5N06TI
- CAS number
- 98-96-4
- Weight
- Average: 123.1127
Monoisotopic: 123.043261797 - Chemical Formula
- C5H5N3O
- InChI Key
- IPEHBUMCGVEMRF-UHFFFAOYSA-N
- InChI
- InChI=1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9)
- IUPAC Name
- pyrazine-2-carboxamide
- SMILES
- NC(=O)C1=NC=CN=C1
Pharmacology
- Indication
For the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents.
- Structured Indications
- Pharmacodynamics
Pyrazinamide kills or stops the growth of certain bacteria that cause tuberculosis (TB). It is used with other drugs to treat tuberculosis. It is a highly specific agent and is active only against Mycobacterium tuberculosis. In vitro and in vivo, the drug is active only at a slightly acid pH. Pyrazinamie gets activated to Pyrazinoic acid in the bacilli where it interferes with fatty acid synthase FAS I. This interferes with the bacteriums ability to synthesize new fatty acids, required for growth and replication.
- Mechanism of action
Pyrazinamide diffuses into M. tuberculosis, where the enzyme pyrazinamidase converts pyrazinamide to the active form pyrazinoic acid. Under acidic conditions, the pyrazinoic acid that slowly leaks out converts to the protonated conjugate acid, which is thought to diffuse easily back into the bacilli and accumulate. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted (PMID: 11914348). However, further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids (PMID: 17101678). This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I (PMID: 17485499).
It has also been suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection.
Pyrazinoic acid has also been shown to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria (PMID: 21835980).
Target Actions Organism AFatty acid synthetase I (FASI) inhibitorMycobacterium tuberculosis - Absorption
Rapidly and well absorbed from the gastrointestinal tract.
- Volume of distribution
- Not Available
- Protein binding
~10% (bound to plasma proteins)
- Metabolism
Hepatic.
Reactions:
- Route of elimination
Approximately 70% of an oral dose is excreted in the urine, mainly by glomerular filtration within 24 hours
- Half life
9-10 hours (normal conditions)
- Clearance
- Not Available
- Toxicity
Side effects include liver injury, arthralgias, anorexia, nausea and vomiting, dysuria,malaise and fever, sideroblastic anemia, adverse effects on the blood clotting mechanism or vascular integrity, and hypersensitivity reactions such as urticaria, pruritis and skin rashes.
- Affected organisms
- Mycobacterium tuberculosis
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Drug group Abiraterone The serum concentration of Pyrazinamide can be increased when it is combined with Abiraterone. Approved Amiodarone The metabolism of Pyrazinamide can be decreased when combined with Amiodarone. Approved, Investigational Aprepitant The serum concentration of Pyrazinamide can be increased when it is combined with Aprepitant. Approved, Investigational Atazanavir The metabolism of Pyrazinamide can be decreased when combined with Atazanavir. Approved, Investigational Atomoxetine The metabolism of Pyrazinamide can be decreased when combined with Atomoxetine. Approved Azithromycin The metabolism of Pyrazinamide can be decreased when combined with Azithromycin. Approved BCG vaccine The therapeutic efficacy of Bcg can be decreased when used in combination with Pyrazinamide. Investigational Bexarotene The serum concentration of Pyrazinamide can be decreased when it is combined with Bexarotene. Approved, Investigational Boceprevir The metabolism of Pyrazinamide can be decreased when combined with Boceprevir. Withdrawn Bortezomib The metabolism of Pyrazinamide can be decreased when combined with Bortezomib. Approved, Investigational Bosentan The serum concentration of Pyrazinamide can be decreased when it is combined with Bosentan. Approved, Investigational Caffeine The metabolism of Pyrazinamide can be decreased when combined with Caffeine. Approved Carbamazepine The metabolism of Pyrazinamide can be increased when combined with Carbamazepine. Approved, Investigational Ceritinib The serum concentration of Pyrazinamide can be increased when it is combined with Ceritinib. Approved Citalopram The metabolism of Pyrazinamide can be decreased when combined with Citalopram. Approved Clarithromycin The metabolism of Pyrazinamide can be decreased when combined with Clarithromycin. Approved Clemastine The metabolism of Pyrazinamide can be decreased when combined with Clemastine. Approved Clotrimazole The metabolism of Pyrazinamide can be decreased when combined with Clotrimazole. Approved, Vet Approved Cobicistat The metabolism of Pyrazinamide can be decreased when combined with Cobicistat. Approved Conivaptan The serum concentration of Pyrazinamide can be increased when it is combined with Conivaptan. Approved, Investigational Crizotinib The metabolism of Pyrazinamide can be decreased when combined with Crizotinib. Approved Cyclosporine The serum concentration of Cyclosporine can be increased when it is combined with Pyrazinamide. Approved, Investigational, Vet Approved Cyclosporine The metabolism of Pyrazinamide can be decreased when combined with Cyclosporine. Approved, Investigational, Vet Approved Cyproterone acetate The serum concentration of Pyrazinamide can be decreased when it is combined with Cyproterone acetate. Approved, Investigational Dabrafenib The serum concentration of Pyrazinamide can be decreased when it is combined with Dabrafenib. Approved Darunavir The metabolism of Pyrazinamide can be decreased when combined with Darunavir. Approved Dasatinib The serum concentration of Pyrazinamide can be increased when it is combined with Dasatinib. Approved, Investigational Deferasirox The serum concentration of Pyrazinamide can be decreased when it is combined with Deferasirox. Approved, Investigational Delavirdine The metabolism of Pyrazinamide can be decreased when combined with Delavirdine. Approved Dexamethasone The serum concentration of Pyrazinamide can be decreased when it is combined with Dexamethasone. Approved, Investigational, Vet Approved Dihydroergotamine The metabolism of Pyrazinamide can be decreased when combined with Dihydroergotamine. Approved Diltiazem The metabolism of Pyrazinamide can be decreased when combined with Diltiazem. Approved Doxycycline The metabolism of Pyrazinamide can be decreased when combined with Doxycycline. Approved, Investigational, Vet Approved Dronedarone The metabolism of Pyrazinamide can be decreased when combined with Dronedarone. Approved Efavirenz The serum concentration of Pyrazinamide can be decreased when it is combined with Efavirenz. Approved, Investigational Enzalutamide The serum concentration of Pyrazinamide can be decreased when it is combined with Enzalutamide. Approved Erythromycin The metabolism of Pyrazinamide can be decreased when combined with Erythromycin. Approved, Vet Approved Eslicarbazepine acetate The serum concentration of Pyrazinamide can be decreased when it is combined with Eslicarbazepine acetate. Approved Etravirine The serum concentration of Pyrazinamide can be decreased when it is combined with Etravirine. Approved Fluconazole The metabolism of Pyrazinamide can be decreased when combined with Fluconazole. Approved Fluvoxamine The metabolism of Pyrazinamide can be decreased when combined with Fluvoxamine. Approved, Investigational Fosamprenavir The metabolism of Pyrazinamide can be decreased when combined with Fosamprenavir. Approved Fosaprepitant The serum concentration of Pyrazinamide can be increased when it is combined with Fosaprepitant. Approved Fosphenytoin The metabolism of Pyrazinamide can be increased when combined with Fosphenytoin. Approved Fusidic Acid The serum concentration of Pyrazinamide can be increased when it is combined with Fusidic Acid. Approved Idelalisib The serum concentration of Pyrazinamide can be increased when it is combined with Idelalisib. Approved Imatinib The metabolism of Pyrazinamide can be decreased when combined with Imatinib. Approved Indinavir The metabolism of Pyrazinamide can be decreased when combined with Indinavir. Approved Isavuconazonium The metabolism of Pyrazinamide can be decreased when combined with Isavuconazonium. Approved, Investigational Isradipine The metabolism of Pyrazinamide can be decreased when combined with Isradipine. Approved Itraconazole The metabolism of Pyrazinamide can be decreased when combined with Itraconazole. Approved, Investigational Ivacaftor The serum concentration of Pyrazinamide can be increased when it is combined with Ivacaftor. Approved Ketoconazole The metabolism of Pyrazinamide can be decreased when combined with Ketoconazole. Approved, Investigational Lidocaine The metabolism of Pyrazinamide can be decreased when combined with Lidocaine. Approved, Vet Approved Lopinavir The metabolism of Pyrazinamide can be decreased when combined with Lopinavir. Approved Lovastatin The metabolism of Pyrazinamide can be decreased when combined with Lovastatin. Approved, Investigational Luliconazole The serum concentration of Pyrazinamide can be increased when it is combined with Luliconazole. Approved Lumacaftor The metabolism of Pyrazinamide can be increased when combined with Lumacaftor. Approved Mexiletine The metabolism of Pyrazinamide can be decreased when combined with Mexiletine. Approved Mifepristone The serum concentration of Pyrazinamide can be increased when it is combined with Mifepristone. Approved, Investigational Mitotane The serum concentration of Pyrazinamide can be decreased when it is combined with Mitotane. Approved Modafinil The serum concentration of Pyrazinamide can be decreased when it is combined with Modafinil. Approved, Investigational Nafcillin The serum concentration of Pyrazinamide can be decreased when it is combined with Nafcillin. Approved Nefazodone The metabolism of Pyrazinamide can be decreased when combined with Nefazodone. Approved, Withdrawn Nelfinavir The metabolism of Pyrazinamide can be decreased when combined with Nelfinavir. Approved Netupitant The serum concentration of Pyrazinamide can be increased when it is combined with Netupitant. Approved Nevirapine The metabolism of Pyrazinamide can be increased when combined with Nevirapine. Approved Nilotinib The metabolism of Pyrazinamide can be decreased when combined with Nilotinib. Approved, Investigational Olaparib The metabolism of Pyrazinamide can be decreased when combined with Olaparib. Approved Osimertinib The serum concentration of Pyrazinamide can be increased when it is combined with Osimertinib. Approved Palbociclib The serum concentration of Pyrazinamide can be increased when it is combined with Palbociclib. Approved Peginterferon alfa-2b The serum concentration of Pyrazinamide can be increased when it is combined with Peginterferon alfa-2b. Approved Pentobarbital The metabolism of Pyrazinamide can be increased when combined with Pentobarbital. Approved, Vet Approved Phenobarbital The metabolism of Pyrazinamide can be increased when combined with Phenobarbital. Approved Phenytoin The metabolism of Pyrazinamide can be increased when combined with Phenytoin. Approved, Vet Approved Picosulfuric acid The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Pyrazinamide. Approved Posaconazole The metabolism of Pyrazinamide can be decreased when combined with Posaconazole. Approved, Investigational, Vet Approved Primidone The metabolism of Pyrazinamide can be increased when combined with Primidone. Approved, Vet Approved Ranolazine The metabolism of Pyrazinamide can be decreased when combined with Ranolazine. Approved, Investigational Rifabutin The metabolism of Pyrazinamide can be increased when combined with Rifabutin. Approved Rifampicin Pyrazinamide may increase the hepatotoxic activities of Rifampicin. Approved Rifapentine The metabolism of Pyrazinamide can be increased when combined with Rifapentine. Approved Ritonavir The metabolism of Pyrazinamide can be decreased when combined with Ritonavir. Approved, Investigational Ropinirole The metabolism of Pyrazinamide can be decreased when combined with Ropinirole. Approved, Investigational Saquinavir The metabolism of Pyrazinamide can be decreased when combined with Saquinavir. Approved, Investigational Sildenafil The metabolism of Pyrazinamide can be decreased when combined with Sildenafil. Approved, Investigational Siltuximab The serum concentration of Pyrazinamide can be decreased when it is combined with Siltuximab. Approved Simeprevir The serum concentration of Pyrazinamide can be increased when it is combined with Simeprevir. Approved St. John's Wort The serum concentration of Pyrazinamide can be decreased when it is combined with St. John's Wort. Nutraceutical Stiripentol The serum concentration of Pyrazinamide can be increased when it is combined with Stiripentol. Approved Sulfisoxazole The metabolism of Pyrazinamide can be decreased when combined with Sulfisoxazole. Approved, Vet Approved Telaprevir The metabolism of Pyrazinamide can be decreased when combined with Telaprevir. Withdrawn Telithromycin The metabolism of Pyrazinamide can be decreased when combined with Telithromycin. Approved Tenofovir disoproxil The metabolism of Pyrazinamide can be decreased when combined with Tenofovir. Approved, Investigational Teriflunomide The serum concentration of Pyrazinamide can be decreased when it is combined with Teriflunomide. Approved Theophylline The metabolism of Pyrazinamide can be decreased when combined with Theophylline. Approved Ticlopidine The metabolism of Pyrazinamide can be decreased when combined with Ticlopidine. Approved Tocilizumab The serum concentration of Pyrazinamide can be decreased when it is combined with Tocilizumab. Approved Vemurafenib The serum concentration of Pyrazinamide can be increased when it is combined with Vemurafenib. Approved Venlafaxine The metabolism of Pyrazinamide can be decreased when combined with Venlafaxine. Approved Verapamil The metabolism of Pyrazinamide can be decreased when combined with Verapamil. Approved Voriconazole The metabolism of Pyrazinamide can be decreased when combined with Voriconazole. Approved, Investigational Ziprasidone The metabolism of Pyrazinamide can be decreased when combined with Ziprasidone. Approved - Food Interactions
- Take without regard to meals.
References
- Synthesis Reference
- Not Available
- General References
- Authors unspecified: Controlled trial of four thrice-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis. Lancet. 1981 Jan 24;1(8213):171-4. [PubMed:6109855 ]
- Authors unspecified: Controlled clinical trial of 4 short-couse regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis. Tubercle. 1983 Sep;64(3):153-66. [PubMed:6356538 ]
- Authors unspecified: A controlled trial of 6 months' chemotherapy in pulmonary tuberculosis. Final report: results during the 36 months after the end of chemotherapy and beyond. British Thoracic Society. Br J Dis Chest. 1984 Oct;78(4):330-6. [PubMed:6386028 ]
- Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D: Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med. 2003 Jun 1;167(11):1472-7. Epub 2003 Jan 31. [PubMed:12569078 ]
- Boshoff HI, Mizrahi V, Barry CE 3rd: Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I. J Bacteriol. 2002 Apr;184(8):2167-72. [PubMed:11914348 ]
- Zimhony O, Vilcheze C, Arai M, Welch JT, Jacobs WR Jr: Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli. Antimicrob Agents Chemother. 2007 Feb;51(2):752-4. Epub 2006 Nov 13. [PubMed:17101678 ]
- Ngo SC, Zimhony O, Chung WJ, Sayahi H, Jacobs WR Jr, Welch JT: Inhibition of isolated Mycobacterium tuberculosis fatty acid synthase I by pyrazinamide analogs. Antimicrob Agents Chemother. 2007 Jul;51(7):2430-5. Epub 2007 May 7. [PubMed:17485499 ]
- Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE 3rd, Wang H, Zhang W, Zhang Y: Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 2011 Sep 16;333(6049):1630-2. doi: 10.1126/science.1208813. Epub 2011 Aug 11. [PubMed:21835980 ]
- External Links
- Human Metabolome Database
- HMDB14483
- KEGG Drug
- D00144
- KEGG Compound
- C01956
- PubChem Compound
- 1046
- PubChem Substance
- 46507478
- ChemSpider
- 1017
- ChEBI
- 45285
- ChEMBL
- CHEMBL614
- Therapeutic Targets Database
- DAP000660
- PharmGKB
- PA451182
- HET
- PZA
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Pyrazinamide
- ATC Codes
- J04AM06 — Rifampicin, pyrazinamide, ethambutol and isoniazid
- J04AM — Combinations of drugs for treatment of tuberculosis
- J04A — DRUGS FOR TREATMENT OF TUBERCULOSIS
- J04 — ANTIMYCOBACTERIALS
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- J04AM — Combinations of drugs for treatment of tuberculosis
- J04A — DRUGS FOR TREATMENT OF TUBERCULOSIS
- J04 — ANTIMYCOBACTERIALS
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- AHFS Codes
- 08:16.04
- PDB Entries
- Not Available
- FDA label
- Not Available
- MSDS
- Download (73.6 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Dava pharmaceuticals inc
- Mikart inc
- Packagers
- Amerisource Health Services Corp.
- A-S Medication Solutions LLC
- Belgomex Sprl
- Cardinal Health
- Comprehensive Consultant Services Inc.
- DAVA Pharmaceuticals
- Dept Health Central Pharmacy
- Mikart Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Physicians Total Care Inc.
- Prescript Pharmaceuticals
- Remedy Repack
- Sanofi-Aventis Inc.
- Versapharm Inc.
- West-Ward Pharmaceuticals
- Dosage forms
Form Route Strength Tablet Oral 500 mg/1 Tablet Oral Tablet, sugar coated Oral Tablet Oral 500 mg - Prices
Unit description Cost Unit Rifater tablet 3.1USD tablet Pyrazinamide 500 mg tablet 1.26USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 192 °C PhysProp water solubility 1.5E+004 mg/L (at 25 °C) MERCK INDEX (1996) logP -0.60 HANSCH,C ET AL. (1995) logS -0.91 ADME Research, USCD pKa -0.5 Not Available - Predicted Properties
Property Value Source Water Solubility 93.7 mg/mL ALOGPS logP -0.71 ALOGPS logP -1.2 ChemAxon logS -0.12 ALOGPS pKa (Strongest Acidic) 13.06 ChemAxon pKa (Strongest Basic) -0.68 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 68.87 Å2 ChemAxon Rotatable Bond Count 1 ChemAxon Refractivity 30.45 m3·mol-1 ChemAxon Polarizability 11.13 Å3 ChemAxon Number of Rings 1 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9813 Blood Brain Barrier + 0.9745 Caco-2 permeable + 0.7222 P-glycoprotein substrate Non-substrate 0.8219 P-glycoprotein inhibitor I Non-inhibitor 0.9709 P-glycoprotein inhibitor II Non-inhibitor 0.9971 Renal organic cation transporter Non-inhibitor 0.8985 CYP450 2C9 substrate Non-substrate 0.8861 CYP450 2D6 substrate Non-substrate 0.876 CYP450 3A4 substrate Non-substrate 0.7754 CYP450 1A2 substrate Non-inhibitor 0.8791 CYP450 2C9 inhibitor Non-inhibitor 0.9545 CYP450 2D6 inhibitor Non-inhibitor 0.9731 CYP450 2C19 inhibitor Non-inhibitor 0.9547 CYP450 3A4 inhibitor Non-inhibitor 0.9697 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9353 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.9321 Biodegradation Not ready biodegradable 0.9602 Rat acute toxicity 1.8145 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9939 hERG inhibition (predictor II) Non-inhibitor 0.9617
Spectra
- Mass Spec (NIST)
- Download (8.68 KB)
- Spectra
Taxonomy
- Description
- This compound belongs to the class of chemical entities known as pyrazines. These are compounds containing a pyrazine ring, which is a six-member aromatic heterocycle, that consists of two nitrogen atoms (at positions 1 and 4) and four carbon atoms.
- Kingdom
- Chemical entities
- Super Class
- Organic compounds
- Class
- Organoheterocyclic compounds
- Sub Class
- Diazines
- Direct Parent
- Pyrazines
- Alternative Parents
- Heteroaromatic compounds / Carboximidic acids / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Hydrocarbon derivatives
- Substituents
- Pyrazine / Heteroaromatic compound / Azacycle / Carboximidic acid derivative / Carboximidic acid / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative / Organooxygen compound
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- pyrazines, monocarboxylic acid amide (CHEBI:45285 ) / a carboxamide (PYRAZINAMIDE )
Targets
1. Fatty acid synthetase I (FASI)
Yes
Inhibitor
References
- Zimhony O, Cox JS, Welch JT, Vilcheze C, Jacobs WR Jr: Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 2000 Sep;6(9):1043-7. [PubMed:10973326 ]
- Ngo SC, Zimhony O, Chung WJ, Sayahi H, Jacobs WR Jr, Welch JT: Inhibition of isolated Mycobacterium tuberculosis fatty acid synthase I by pyrazinamide analogs. Antimicrob Agents Chemother. 2007 Jul;51(7):2430-5. Epub 2007 May 7. [PubMed:17485499 ]
- Zimhony O, Vilcheze C, Arai M, Welch JT, Jacobs WR Jr: Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli. Antimicrob Agents Chemother. 2007 Feb;51(2):752-4. Epub 2006 Nov 13. [PubMed:17101678 ]
- Schroeder EK, de Souza N, Santos DS, Blanchard JS, Basso LA: Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis. Curr Pharm Biotechnol. 2002 Sep;3(3):197-225. [PubMed:12164478 ]
Enzymes
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xanthine oxidase activity
- Specific Function
- Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
- Gene Name
- XDH
- Uniprot ID
- P47989
- Uniprot Name
- Xanthine dehydrogenase/oxidase
- Molecular Weight
- 146422.99 Da
References
- Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochem Pharmacol. 1993 Sep 14;46(6):975-81. [PubMed:8216357 ]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xanthine dehydrogenase activity
- Specific Function
- Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
- Gene Name
- AOX1
- Uniprot ID
- Q06278
- Uniprot Name
- Aldehyde oxidase
- Molecular Weight
- 147916.735 Da
References
- Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochem Pharmacol. 1993 Sep 14;46(6):975-81. [PubMed:8216357 ]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- 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 performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Drug created on June 13, 2005 07:24 / Updated on September 01, 2017 10:26