FRCD

Common Name	Isobergapten(F03905)
2D Structure
Description	Isobergapten is a furocoumarin. Furocoumarins, are phototoxic and photocarcinogenic. They intercalate DNA and photochemically induce mutations. Furocoumarins are botanical phytoalexins found to varying extents in a variety of vegetables and fruits, notably citrus fruits. The levels of furocoumarins present in our diets, while normally well below that causing evident acute phototoxicity, do cause pharmacologically relevant drug interactions. Some are particularly active against cytochrome P450s. For example, in humans, bergamottin and dihydroxybergamottin are responsible for the 'grapefruit juice effect', in which these furanocoumarins affect the metabolism of certain drugs.
FRCD ID	F03905
CAS Number	482-48-4
PubChem CID	68082
Formula	C12H8O4
IUPAC Name	5-methoxyfuro[2,3-h]chromen-2-one
InChI Key	AJSPSRWWZBBIOR-UHFFFAOYSA-N
InChI	InChI=1S/C12H8O4/c1-14-9-6-10-8(4-5-15-10)12-7(9)2-3-11(13)16-12/h2-6H,1H3
Canonical SMILES	COC1=C2C=CC(=O)OC2=C3C=COC3=C1
Isomeric SMILES	COC1=C2C=CC(=O)OC2=C3C=COC3=C1
Synonyms	Isobergaptene 2H-Furo[2,3-h]-1-benzopyran-2-one, 5-methoxy- Isobergapten 482-48-4 5-Methoxy-2H-furo[2,3-H]chromen-2-one UNII-27X3V737WH CHEBI:81487 27X3V737WH 5-methoxyfuro[2,3-h]chromen-2-one 2H-Furo(2,3-h)-1-benzopyran-2-one, 5-methoxy-
Classifies	Plant Toxin
Update Date	Nov 13, 2018 17:07

Kingdom	Organic compounds
Superclass	Phenylpropanoids and polyketides
Class	Coumarins and derivatives
Subclass	Furanocoumarins
Intermediate Tree Nodes	Not available
Direct Parent	Angular furanocoumarins
Alternative Parents	Hydrocarbon derivatives Organic oxides Alkyl aryl ethers Oxacyclic compounds Anisoles Furans Heteroaromatic compounds 1-benzopyrans Lactones Pyranones and derivatives Benzofurans
Molecular Framework	Aromatic heteropolycyclic compounds
Substituents	Angular furanocoumarin - Benzopyran - 1-benzopyran - Benzofuran - Anisole - Alkyl aryl ether - Pyranone - Pyran - Benzenoid - Furan - Heteroaromatic compound - Lactone - Oxacycle - Ether - Organoheterocyclic compound - Organic oxygen compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Aromatic heteropolycyclic compound
Description	This compound belongs to the class of organic compounds known as angular furanocoumarins. These are furanocoumarins, with a structure characterized by a furan ring angularly fused to a coumarin.

Property Name	Property Value
Molecular Weight	216.192
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Complexity	325
Monoisotopic Mass	216.042
Exact Mass	216.042
XLogP	2
Formal Charge	0
Heavy Atom Count	16
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.9254
Human Intestinal Absorption	HIA+	0.9933
Caco-2 Permeability	Caco2+	0.6835
P-glycoprotein Substrate	Non-substrate	0.5685
P-glycoprotein Inhibitor	Non-inhibitor	0.6457
P-glycoprotein Inhibitor	Non-inhibitor	0.6475
Renal Organic Cation Transporter	Non-inhibitor	0.8026
Distribution
Subcellular localization	Mitochondria	0.6414
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.7803
CYP450 2D6 Substrate	Non-substrate	0.9085
CYP450 3A4 Substrate	Non-substrate	0.6413
CYP450 1A2 Inhibitor	Inhibitor	0.9774
CYP450 2C9 Inhibitor	Inhibitor	0.8257
CYP450 2D6 Inhibitor	Inhibitor	0.8931
CYP450 2C19 Inhibitor	Inhibitor	0.9296
CYP450 3A4 Inhibitor	Inhibitor	0.7959
CYP Inhibitory Promiscuity	High CYP Inhibitory Promiscuity	0.7435
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9144
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9676
AMES Toxicity	AMES toxic	0.9107
Carcinogens	Non-carcinogens	0.9517
Fish Toxicity	High FHMT	0.9404
Tetrahymena Pyriformis Toxicity	High TPT	0.9852
Honey Bee Toxicity	High HBT	0.8462
Biodegradation	Not ready biodegradable	0.6650
Acute Oral Toxicity	III	0.5714
Carcinogenicity (Three-class)	Warning	0.4707

Model	Value	Unit
Absorption
Aqueous solubility	-3.5245	LogS
Caco-2 Permeability	0.9033	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.2791	LD50, mol/kg
Fish Toxicity	-0.2970	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.7820	pIGC50, ug/L

Targets

General Function:: Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:: CYP2C9
Uniprot ID:: P11712
Molecular Weight:: 55627.365 Da

Girennavar B, Jayaprakasha GK, Patil BS: Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins. J Food Sci. 2007 Oct;72(8):C417-21. [17995595 ]

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:: CYP3A4
Uniprot ID:: P08684
Molecular Weight:: 57342.67 Da

Girennavar B, Jayaprakasha GK, Patil BS: Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins. J Food Sci. 2007 Oct;72(8):C417-21. [17995595 ]