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Identification
NameTrioxsalen
Accession NumberDB04571
TypeSmall Molecule
GroupsApproved
Description

Trioxsalen (trimethylpsoralen, trioxysalen or trisoralen) is a furanocoumarin and a psoralen derivative. It is obtained from several plants, mainly Psoralea corylifolia. Like other psoralens it causes photosensitization of the skin. It is administered either topically or orally in conjunction with UV-A (the least damaging form of ultraviolet light) for phototherapy treatment of vitiligo1 and hand eczema.2 After photoactivation it creates interstrand cross-links in DNA, which can cause programmed cell death unless repaired by cellular mechanisms. In research it can be conjugated to dyes for confocal microscopy and used to visualize sites of DNA damage.3 The compound is also being explored for development of antisense oligonucleotides that can be cross-linked specifically to a mutant mRNA sequence without affecting normal transcripts differing at even a single base pair.

Structure
Thumb
Synonyms
SynonymLanguageCode
2',4,8-TrimethylpsoralenNot AvailableNot Available
4,5',8-TrimethylpsoralenNot AvailableNot Available
4,8,5'-TrimethylpsoralenNot AvailableNot Available
6-Hydroxy-beta,2,7-trimethyl-5-benzofuranacrylic acid, delta-lactoneNot AvailableNot Available
trimethylpsoralenNot AvailableNot Available
TrioxisalenoNot AvailableNot Available
TrioxsalenNot AvailableNot Available
trioxysalenNot AvailableNot Available
TrioxysaleneNot AvailableNot Available
TrioxysalenumNot AvailableNot Available
trisoralenNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number3902-71-4
WeightAverage: 228.2433
Monoisotopic: 228.07864425
Chemical FormulaC14H12O3
InChI KeyFMHHVULEAZTJMA-UHFFFAOYSA-N
InChI
InChI=1S/C14H12O3/c1-7-4-12(15)17-14-9(3)13-10(6-11(7)14)5-8(2)16-13/h4-6H,1-3H3
IUPAC Name
2,5,9-trimethyl-7H-furo[3,2-g]chromen-7-one
SMILES
CC1=CC2=CC3=C(OC(=O)C=C3C)C(C)=C2O1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as linear furanocoumarins. These are furanocoumarins, with a structure characterized by a furan ring linearly fused to a coumarin.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCoumarins and derivatives
Sub ClassFuranocoumarins
Direct ParentLinear furanocoumarins
Alternative Parents
Substituents
  • Linear furanocoumarin
  • Psoralen
  • 1-benzopyran
  • Benzopyran
  • Benzofuran
  • Pyranone
  • Benzenoid
  • Pyran
  • Heteroaromatic compound
  • Furan
  • Lactone
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationTrioxsalen is a pigmenting photosensitizing agent used in conjunction with ultraviolet light in the treatment of vitiligo.
PharmacodynamicsTrioxsalen ispharmacologically inactive but when exposed to ultraviolet radiation or sunlight it is converted to its active metabolite to produce a beneficial reaction affecting the diseased tissue.
Mechanism of actionAfter photoactivation it creates interstrand cross-links in DNA, which can cause programmed cell death.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9972
Blood Brain Barrier+0.948
Caco-2 permeable+0.6552
P-glycoprotein substrateNon-substrate0.6143
P-glycoprotein inhibitor INon-inhibitor0.5919
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8471
CYP450 2C9 substrateNon-substrate0.7878
CYP450 2D6 substrateNon-substrate0.8831
CYP450 3A4 substrateNon-substrate0.6234
CYP450 1A2 substrateInhibitor0.9217
CYP450 2C9 substrateNon-inhibitor0.9071
CYP450 2D6 substrateNon-inhibitor0.8415
CYP450 2C19 substrateNon-inhibitor0.7328
CYP450 3A4 substrateInhibitor0.6141
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6083
Ames testNon AMES toxic0.8038
CarcinogenicityNon-carcinogens0.9169
BiodegradationNot ready biodegradable0.8998
Rat acute toxicity1.6608 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9098
hERG inhibition (predictor II)Non-inhibitor0.9549
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point234.5 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0627 mg/mLALOGPS
logP3.26ALOGPS
logP2.95ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area39.44 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity64.86 m3·mol-1ChemAxon
Polarizability24.77 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.79 KB)
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. van Coevorden AM, Kamphof WG, van Sonderen E, Bruynzeel DP, Coenraads PJ: Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema: an open-label randomized controlled trial of efficacy. Arch Dermatol. 2004 Dec;140(12):1463-6. Pubmed
  2. Thazhathveetil AK, Liu ST, Indig FE, Seidman MM: Psoralen conjugates for visualization of genomic interstrand cross-links localized by laser photoactivation. Bioconjug Chem. 2007 Mar-Apr;18(2):431-7. Pubmed
  3. Higuchi M, Yamayoshi A, Kobori A, Yamaoka T, Murakami A: Synthesis and properties of photo-reactive antisense oligonucleotides containing 2’-O-psoralen-conjugated adenosine. Nucleic Acids Symp Ser (Oxf). 2005;(49):331-2. Pubmed
External Links
ATC CodesD05AD01D05BA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
PorfimerMay enhance the photosensitizing effect of Porfimer.
VerteporfinMay enhance the photosensitizing effect of Verteporfin.
Food Interactions
  • avoid eating limes, figs, parsley, parsnips, mustard, carrots, and celery while you are being treated with trioxsalen

Targets

1. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: cross-linking/alkylation

Components

Name UniProt ID Details

References:

  1. Thazhathveetil AK, Liu ST, Indig FE, Seidman MM: Psoralen conjugates for visualization of genomic interstrand cross-links localized by laser photoactivation. Bioconjug Chem. 2007 Mar-Apr;18(2):431-7. Pubmed
  2. Vasquez KM, Wensel TG, Hogan ME, Wilson JH: High-efficiency triple-helix-mediated photo-cross-linking at a targeted site within a selectable mammalian gene. Biochemistry. 1996 Aug 20;35(33):10712-9. Pubmed
  3. Dardare N, Platz MS: Binding affinities of commonly employed sensitizers of viral inactivation. Photochem Photobiol. 2002 Jun;75(6):561-4. Pubmed
  4. Jimenez-Ruiz A, Zhang Q, Shen CK: In vivo binding of trimethylpsoralen detects DNA structural alterations associated with transcribing regions in the human beta-globin cluster. J Biol Chem. 1995 Dec 1;270(48):28978-81. Pubmed

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Drug created on September 07, 2007 14:54 / Updated on September 16, 2013 17:25