Trioxsalen

Identification

Name
Trioxsalen
Accession Number
DB04571
Type
Small Molecule
Groups
Approved
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 vitiligo[1] 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
  • 2',4,8-Trimethylpsoralen
  • 4,5',8-Trimethylpsoralen
  • 4,8,5'-Trimethylpsoralen
  • 6-Hydroxy-beta,2,7-trimethyl-5-benzofuranacrylic acid, delta-lactone
  • trimethylpsoralen
  • Trioxisaleno
  • Trioxsalen
  • trioxysalen
  • Trioxysalene
  • Trioxysalenum
  • trisoralen
External IDs
NSC-71047
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Trisoralen Tab 5mgTablet5 mgOralIcn Pharmaceuticals1993-12-312005-04-26Canada
Categories
UNII
Y6UY8OV51T
CAS number
3902-71-4
Weight
Average: 228.2433
Monoisotopic: 228.07864425
Chemical Formula
C14H12O3
InChI Key
FMHHVULEAZTJMA-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

Pharmacology

Indication

Trioxsalen is a pigmenting photosensitizing agent used in conjunction with ultraviolet light in the treatment of vitiligo.

Pharmacodynamics

Trioxsalen 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 action

After photoactivation it creates interstrand cross-links in DNA, which can cause programmed cell death.

TargetActionsOrganism
ADNA
cross-linking/alkylation
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Porfimer sodiumTrioxsalen may increase the photosensitizing activities of Porfimer sodium.
VerteporfinTrioxsalen may increase the photosensitizing activities of Verteporfin.
Food Interactions
  • avoid eating limes, figs, parsley, parsnips, mustard, carrots, and celery while you are being treated with trioxsalen

References

General References
  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:15611423]
  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:17373769]
  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:17150768]
External Links
Human Metabolome Database
HMDB0015575
KEGG Drug
D01034
KEGG Compound
C09314
PubChem Compound
5585
PubChem Substance
46508755
ChemSpider
5383
ChEBI
28329
ChEMBL
CHEMBL1475
PharmGKB
PA164747186
Drugs.com
Drugs.com Drug Page
Wikipedia
Trioxsalen
ATC Codes
D05AD01 — TrioxysalenD05BA01 — Trioxysalen

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral5 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)234.5 °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 RuleNoChemAxon
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 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.8415
CYP450 2C19 inhibitorNon-inhibitor0.7328
CYP450 3A4 inhibitorInhibitor0.6141
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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.79 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as psoralens. These are organic compounds containing a psoralen moiety, which consists of a furan fused to a chromenone to for 7H-furo[3,2-g]chromen-7-one.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Coumarins and derivatives
Sub Class
Furanocoumarins
Direct Parent
Psoralens
Alternative Parents
1-benzopyrans / Benzofurans / Pyranones and derivatives / Benzenoids / Heteroaromatic compounds / Furans / Lactones / Oxacyclic compounds / Organooxygen compounds / Organic oxides
show 1 more
Substituents
Psoralen / Benzopyran / 1-benzopyran / Benzofuran / Pyranone / Benzenoid / Pyran / Furan / Heteroaromatic compound / Lactone
show 7 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
psoralens (CHEBI:28329) / Furanocoumarins (C09314)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Cross-linking/alkylation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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:17373769]
  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:8718860]
  3. Dardare N, Platz MS: Binding affinities of commonly employed sensitizers of viral inactivation. Photochem Photobiol. 2002 Jun;75(6):561-4. [PubMed:12081315]
  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:7499429]

Drug created on September 07, 2007 14:54 / Updated on November 02, 2018 06:01