FURAFYLLINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H12N4O3
Molecular Weight	260.2487
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(=O)N(CC2=CC=CO2)C3=C(NC(C)=N3)C1=O

InChI

InChIKey=KGQZGCIVHYLPBH-UHFFFAOYSA-N

InChI=1S/C12H12N4O3/c1-7-13-9-10(14-7)16(6-8-4-3-5-19-8)12(18)15(2)11(9)17/h3-5H,6H2,1-2H3,(H,13,14)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2378786 | https://www.ncbi.nlm.nih.gov/pubmed/3814465

Furafylline is a methylxanthine derivative that was introduced as a long-acting replacement for theophylline in the treatment of asthma, it was a bronchodilator with extended duration compared to theophylline, but then subsequently reported the adverse side effects the inhibition of the oxidation of caffeine, a reaction catalyzed by CYP1A2. Furafylline is now widely used in biochemical studies as a selective mechanism-based inhibitor of cytochrome p450 1A2.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 1A2 73 Target ID: P05177 Gene ID: 1544.0 Gene Symbol: CYP1A2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/2378786	Inhibitor 8504		0.07 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2596

PubMed

Title	Date	PubMed
DNA adducts of the tobacco carcinogens 2-amino-9H-pyrido[2,3-b]indole and 4-aminobiphenyl are formed at environmental exposure levels and persist in human hepatocytes.	2013-09-16	23898916
Interactions of sesquiterpenes zederone and germacrone with the human cytochrome P450 system.	2013-09	23850985
Non-dioxin-like AhR ligands in a mouse peanut allergy model.	2012-07	22491429
Role of P450 1A1 and P450 1A2 in bioactivation versus detoxication of the renal carcinogen aristolochic acid I: studies in Cyp1a1-/-, Cyp1a2-/-, and Cyp1a1/1a2-/- mice.	2011-10-17	21932800
Characterization of glutathione conjugates of duloxetine by mass spectrometry and evaluation of in silico approaches to rationalize the site of conjugation for thiophene containing drugs.	2010-08-16	20669986
Comparative study of the oxidation of propranolol enantiomers in hepatic and small intestinal microsomes from cynomolgus and marmoset monkeys.	2010-01-05	19853591
Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite.	2010-01	19812348
Functional expression, inhibition and induction of CYP enzymes in HepaRG cells.	2009-06	19328226
In vitro nimesulide studies toward understanding idiosyncratic hepatotoxicity: diiminoquinone formation and conjugation.	2009-01	19053182
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.	2008-12	18493746
Automated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis.	2005-11	16049126
Characterization of microsomal cytochrome P450-dependent monooxygenases in the rat olfactory mucosa.	2005-08	15879494
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.	2005-08	15860655
Rate-limiting biotransformation of triamterene is mediated by CYP1A2.	2005-07	16035375
Molecular cloning and functional analysis of cytochrome P450 1A2 from Japanese monkey liver: comparison with marmoset cytochrome P450 1A2.	2005-02-28	15766918
Metabolism of territrem B and C in liver microsomes from 14-wk-old Wistar rats is catalyzed by cytochrome P-450 3A.	2005-02-27	15799453
Cytochromes 1A1/1B1- and catechol-O-methyltransferase-derived metabolites mediate estradiol-induced antimitogenesis in human cardiac fibroblast.	2005-01	15507517
Effects of avasimibe on cytochrome P450 2C9 expression in vitro and in vivo.	2004-12	15333513
Drug-drug interactions of Z-338, a novel gastroprokinetic agent, with terfenadine, comparison with cisapride, and involvement of UGT1A9 and 1A8 in the human metabolism of Z-338.	2004-08-23	15306208
Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomes.	2004-08-15	15276085
Identification of cytochrome P-450s involved in the formation of APNH from norharman with aniline.	2004-08-08	15279827
Validated assays for human cytochrome P450 activities.	2004-06	15155557
Selectivities of human cytochrome P450 inhibitors toward rat P450 isoforms: study with cDNA-expressed systems of the rat.	2003-07	12814958
High-throughput inhibition screening of major human cytochrome P450 enzymes using an in vitro cocktail and liquid chromatography-tandem mass spectrometry.	2003-01-01	12467917
Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate.	2003	12569440
Azole-antifungal binding to a novel cytochrome P450 from Mycobacterium tuberculosis: implications for treatment of tuberculosis.	2001-06-15	11377375
Cytochrome P450 isoform selectivity in human hepatic theobromine metabolism.	1999-03	10215755
Identification of enzymes involved in the metabolism of atrazine, terbuthylazine, ametryne, and terbutryne in human liver microsomes.	1997-09	9305587
Assessing human risk to heterocyclic amines.	1997-05-12	9202738
Human cytochrome P450 isoform specificity in the regioselective metabolism of toluene and o-, m- and p-xylene.	1996-01	8558417
Metabolism of the food derived mutagen and carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) by human liver microsomes.	1994-06	8020169

Patents

Sample Use Guides

In Vivo Use Guide

in normal volunteers: steady state was achieved on the first day following the administration of 90 mg and maintained by subsequent daily doses of 30 mg.

Route of Administration: Oral

In Vitro Use Guide

Furafylline was a potent, non-competitive inhibitor of high affinity phenacetin O-deethylase activity of microsomal fractions of human liver, a reaction catalysed by P450IA2, with an IC50 value of 0.07 microM. Furafylline was added to the samples at a concentration of 0-200 um. Furafylline had either very little or no effect on human monooxygenase activities catalysed by other isoenzymes of P450, including P450IID1, P450IIC, P450IIA.

Name

Type

Language

FURAFYLLINE

Official Name

English

Furafylline [WHO-DD]

Preferred Name

English

furafylline [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C744