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 72 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 8297		0.07 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

PubMed

Title	Date	PubMed
Metabolism of the food derived mutagen and carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) by human liver microsomes.	1994 Jun	8020169
Human cytochrome P450 isoform specificity in the regioselective metabolism of toluene and o-, m- and p-xylene.	1996 Jan	8558417
Assessing human risk to heterocyclic amines.	1997 May 12	9202738
Identification of enzymes involved in the metabolism of atrazine, terbuthylazine, ametryne, and terbutryne in human liver microsomes.	1997 Sep	9305587
Cytochrome P450 isoform selectivity in human hepatic theobromine metabolism.	1999 Mar	10215755
Azole-antifungal binding to a novel cytochrome P450 from Mycobacterium tuberculosis: implications for treatment of tuberculosis.	2001 Jun 15	11377375
Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate.	2003	12569440
High-throughput inhibition screening of major human cytochrome P450 enzymes using an in vitro cocktail and liquid chromatography-tandem mass spectrometry.	2003 Jan 1	12467917
Selectivities of human cytochrome P450 inhibitors toward rat P450 isoforms: study with cDNA-expressed systems of the rat.	2003 Jul	12814958
Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomes.	2004 Aug 15	15276085
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 Aug 23	15306208
Identification of cytochrome P-450s involved in the formation of APNH from norharman with aniline.	2004 Aug 8	15279827
Validated assays for human cytochrome P450 activities.	2004 Jun	15155557
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.	2005 Aug	15860655
Metabolism of territrem B and C in liver microsomes from 14-wk-old Wistar rats is catalyzed by cytochrome P-450 3A.	2005 Feb 27	15799453
Rate-limiting biotransformation of triamterene is mediated by CYP1A2.	2005 Jul	16035375
Automated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis.	2005 Nov	16049126
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.	2008 Dec	18493746
In vitro nimesulide studies toward understanding idiosyncratic hepatotoxicity: diiminoquinone formation and conjugation.	2009 Jan	19053182
Functional expression, inhibition and induction of CYP enzymes in HepaRG cells.	2009 Jun	19328226
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 Oct 17	21932800
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 Sep 16	23898916

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 [INN]

Common Name

English

Furafylline [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C744