FRCD

Common Name	Heratomin(F03907)
2D Structure
Description	Heratomin 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	F03907
CAS Number	61265-06-3
PubChem CID	181312
Formula	C16H14O4
IUPAC Name	6-(3-methylbut-2-enoxy)furo[2,3-h]chromen-2-one
InChI Key	DSDJMMMGDPDPIX-UHFFFAOYSA-N
InChI	InChI=1S/C16H14O4/c1-10(2)5-7-18-13-9-11-3-4-14(17)20-15(11)12-6-8-19-16(12)13/h3-6,8-9H,7H2,1-2H3
Canonical SMILES	CC(=CCOC1=C2C(=C3C(=C1)C=CC(=O)O3)C=CO2)C
Isomeric SMILES	CC(=CCOC1=C2C(=C3C(=C1)C=CC(=O)O3)C=CO2)C
Synonyms	AC1L48SW 2H-Furo(2,3-h)-1-benzopyran-2-one, 6-((3-methyl-2-butenyl)oxy)- HERATOMIN 61265-06-3 ZINC5158821 6-(3-methylbut-2-enoxy)furo[2,3-h]chromen-2-one
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 Furans Heteroaromatic compounds Benzenoids 1-benzopyrans Lactones Pyranones and derivatives Benzofurans
Molecular Framework	Aromatic heteropolycyclic compounds
Substituents	Angular furanocoumarin - Benzopyran - 1-benzopyran - Benzofuran - Alkyl aryl ether - Pyranone - Benzenoid - Pyran - Heteroaromatic compound - Furan - Lactone - Ether - Organoheterocyclic compound - Oxacycle - 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	270.284
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Complexity	436
Monoisotopic Mass	270.089
Exact Mass	270.089
XLogP	3.8
Formal Charge	0
Heavy Atom Count	20
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+	0.8298
Human Intestinal Absorption	HIA+	0.9962
Caco-2 Permeability	Caco2-	0.5187
P-glycoprotein Substrate	Substrate	0.6670
P-glycoprotein Inhibitor	Inhibitor	0.8783
P-glycoprotein Inhibitor	Inhibitor	0.7308
Renal Organic Cation Transporter	Non-inhibitor	0.7391
Distribution
Subcellular localization	Mitochondria	0.7743
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8374
CYP450 2D6 Substrate	Non-substrate	0.8840
CYP450 3A4 Substrate	Substrate	0.5656
CYP450 1A2 Inhibitor	Inhibitor	0.8503
CYP450 2C9 Inhibitor	Inhibitor	0.7199
CYP450 2D6 Inhibitor	Inhibitor	0.7115
CYP450 2C19 Inhibitor	Inhibitor	0.8977
CYP450 3A4 Inhibitor	Inhibitor	0.7497
CYP Inhibitory Promiscuity	High CYP Inhibitory Promiscuity	0.9360
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9522
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.8890
AMES Toxicity	AMES toxic	0.9107
Carcinogens	Non-carcinogens	0.9385
Fish Toxicity	High FHMT	0.9951
Tetrahymena Pyriformis Toxicity	High TPT	0.9919
Honey Bee Toxicity	High HBT	0.8870
Biodegradation	Not ready biodegradable	0.7509
Acute Oral Toxicity	III	0.6516
Carcinogenicity (Three-class)	Non-required	0.5712

Model	Value	Unit
Absorption
Aqueous solubility	-4.1536	LogS
Caco-2 Permeability	0.8364	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.7972	LD50, mol/kg
Fish Toxicity	-1.4952	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.6404	pIGC50, ug/L

Targets

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 ]

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 ]