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Details

Stereochemistry ACHIRAL
Molecular Formula C12H8O4
Molecular Weight 216.1895
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHOXSALEN

SMILES

COC1=C2OC=CC2=CC3=C1OC(=O)C=C3

InChI

InChIKey=QXKHYNVANLEOEG-UHFFFAOYSA-N
InChI=1S/C12H8O4/c1-14-12-10-8(4-5-15-10)6-7-2-3-9(13)16-11(7)12/h2-6H,1H3

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB00553 https://en.wikipedia.org/wiki/Methoxsalen

Methoxsalen — also called xanthotoxin, marketed under the trade names Oxsoralen, Deltasoralen, Meladinine — is a drug used to treat psoriasis, eczema, vitiligo, and some cutaneous lymphomas in conjunction with exposing the skin to UVA light from lamps or sunlight. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. The dosage comes in 10 mg tablets, which are taken in the amount of 30 mg 75 minutes before a PUVA (psoralen + UVA) light treatment. Chemically, methoxsalen belongs to a class of organic natural molecules known as furanocoumarins. They consist of coumarin annulated with furan. It can also be injected and used topically. The exact mechanism of action of methoxsalen with the epidermal melanocytes and keratinocytes is not known. The best known biochemical reaction of methoxsalen is with DNA. Methoxsalen, upon photoactivation, conjugates and forms covalent bonds with DNA which leads to the formation of both monofunctional (addition to a single strand of DNA) and bifunctional adducts (crosslinking of psoralen to both strands of DNA) Reactions with proteins have also been described. Methoxsalen acts as a photosensitizer. Administration of the drug and subsequent exposure to UVA can lead to cell injury. Orally administered methoxsalen reaches the skin via the blood and UVA penetrates well into the skin. If sufficient cell injury occurs in the skin, an inflammatory reaction occurs. The most obvious manifestation of this reaction is delayed erythema, which may not begin for several hours and peaks at 48–72 hours. The inflammation is followed, over several days to weeks, by repair which is manifested by increased melanization of the epidermis and thickening of the stratum corneum. The mechanisms of therapy are not known. In the treatment of vitiligo, it has been suggested that melanocytes in the hair follicle are stimulated to move up the follicle and to repopulate the epidermis. In the treatment of psoriasis, the mechanism is most often assumed to be DNA photodamage and resulting decrease in cell proliferation but other vascular, leukocyte, or cell regulatory mechanisms may also be playing some role. Psoriasis is a hyperproliferative disorder and other agents known to be therapeutic for psoriasis are known to inhibit DNA synthesis. The most commonly reported side effect of methoxsalen alone is nausea, which occurs with approximately 10% of all patients. This effect may be minimized or avoided by instructing the patient to take methoxsalen with milk or food, or to divide the dose into two portions, taken approximately one-half hour apart. Other effects include nervousness, insomnia, and psychological depression.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
8-MOP

Approved Use

when the diagnosis has been supported by biopsy. Photochemotherapy is intended to be administered only in conjunction with a schedule of controlled doses of long wave ultraviolet radiation.

Launch Date

1954
Primary
8-MOP

Approved Use

Photochemotherapy (methoxsalen with long wave ultraviolet radiation) is indicated for the repigmentation of idiopathic vitiligo

Launch Date

1954
Palliative
8-MOP

Approved Use

in the palliative treatment of the skin manifestations of cutaneous T-cell lymphoma (CTCL) in persons who have not been responsive to other forms of treatment. While this dosage form of methoxsalen has been approved for use in combination with photopheresis, Oxsoralen Ultra Capsules have not been approved for that use.

Launch Date

1954
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
129 ng/mL
0.6 mg/kg single, oral
dose: 0.6 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHOXSALEN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
521 ng × h/mL
0.6 mg/kg single, oral
dose: 0.6 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHOXSALEN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.38 h
0.6 mg/kg single, oral
dose: 0.6 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHOXSALEN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
0.6 mg/kg 4 times / week multiple, oral
Recommended
Dose: 0.6 mg/kg, 4 times / week
Route: oral
Route: multiple
Dose: 0.6 mg/kg, 4 times / week
Sources: Page: p.103
unhealthy, 49.7
n = 14
Health Status: unhealthy
Condition: Palmoplantar eczema
Age Group: 49.7
Sex: M+F
Population Size: 14
Sources: Page: p.103
70 mg 4 times / week multiple, oral (max)
Recommended
Dose: 70 mg, 4 times / week
Route: oral
Route: multiple
Dose: 70 mg, 4 times / week
Co-administed with::
UVA
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Psoriasis
Sources: Page: p.5
Disc. AE: Cataract...
AEs leading to
discontinuation/dose reduction:
Cataract
Sources: Page: p.5
AEs

AEs

AESignificanceDosePopulation
Cataract Disc. AE
70 mg 4 times / week multiple, oral (max)
Recommended
Dose: 70 mg, 4 times / week
Route: oral
Route: multiple
Dose: 70 mg, 4 times / week
Co-administed with::
UVA
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Psoriasis
Sources: Page: p.5
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
yes [IC50 2 uM]
yes [Ki 0.11 uM]
yes [Ki 0.2 uM]
yes [Ki 0.8 uM]
yes [Ki 20 uM]
yes [Ki 20 uM]
yes [Ki 25 uM]
yes [Ki 3 uM]
yes [Ki 35 uM]
yes [Ki 75 uM]
yes
yes
yes
Drug as victim

Drug as victim

Tox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Metabolism of 3-methylindole by porcine liver microsomes: responsible cytochrome P450 enzymes.
2000 Jun
The coumarin osthol attenuates the binding of thyrotropin-releasing hormone in rat pituitary GH4C1 cells.
2001 Apr
Expression of CYP6B1 and CYP6B3 cytochrome P450 monooxygenases and furanocoumarin metabolism in different tissues of Papilio polyxenes (Lepidoptera: Papilionidae).
2001 Apr 27
Can a mixed damage interfere with DNA-protein cross-links repair?
2001 Apr-Jun
Plasma and skin concentration of 5-methoxypsoralen in psoriatic patients after oral administration.
2001 Aug
Halothane-dependent lipid peroxidation in human liver microsomes is catalyzed by cytochrome P4502A6 (CYP2A6).
2001 Aug
Does the minimal phototoxic dose after 8-methoxypsoralen baths correlate with the individual's skin phototype?
2001 Aug
Systemic allergic contact dermatitis to 8-methoxypsoralen (8-MOP).
2001 Dec
S. cerevisiae has three pathways for DNA interstrand crosslink repair.
2001 Dec 19
Induction of unscheduled DNA synthesis in hairless mouse epidermis by 8-methoxypsoralen plus ultraviolet A (PUVA).
2001 Feb
Pharmacokinetic behaviour of sublingually administered 8-methoxypsoralen for PUVA therapy.
2001 Feb
A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s using an in vitro cocktail of probe substrates and fast gradient liquid chromatography tandem mass spectrometry.
2001 Jan
Localized vitiligo successfully treated with cream-psoralen + ultraviolet A.
2001 Jul
What's new in the treatment of vitiligo.
2001 Jul
Furanochromone radical cations: generation, characterization and interaction with DNA.
2001 Jul 2
Furanocoumarins in celery and parsnips: method and multiyear Canadian survey.
2001 Jul-Aug
Penetration kinetics of 8-methoxypsoralen after 8-methoxypsoralen bath procedure with and without UVA irradiation.
2001 Jul-Aug
Kinetics of phototoxicity in trioxysalen bath psoralen plus ultraviolet A photochemotherapy.
2001 Jun-Jul
The effect of methoxsalen dose on ultraviolet-A-induced erythema.
2001 May
Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists.
2001 Nov
A bioassay using the human hepatoblastoma cell line HepG2 for detecting phototoxicity of furocoumarins.
2001 Oct
Effects of phytic acid and xanthotoxin on growth and detoxification in caterpillars.
2001 Sep
Photoclastogenicity-an improved protocol, its validation, and investigation of the photogenotoxicity of DMBA.
2002
Characteristics of photopheresis treatments for the management of rejection in heart and lung transplant recipients.
2002
Mitochondrial alterations in fanconi anemia fibroblasts following ultraviolet A or psoralen photoactivation.
2002 Feb
Effects of the isoflavone 4',5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage.
2002 Feb
Cell-impermeant pyridinium derivatives of psoralens as inhibitors of keratinocyte growth.
2002 Jan 1
Changes in skin physiology during bath PUVA therapy.
2002 Jul
T cell clonality and the effect of photopheresis in systemic sclerosis and graft versus host disease.
2002 Jun
Transimmunization and the evolution of extracorporeal photochemotherapy.
2002 Jun
A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in vitro.
2002 Jun 15
Time course of 8-methoxypsoralen concentrations in skin and plasma after topical (bath and cream) and oral administration of 8-methoxypsoralen.
2002 Mar
Decreased survival of UV-irradiated Staphylococcus aureus in the presence of 8-methoxypsoralen in the post-irradiation plating medium.
2002 Mar
Bullous phytophotodermatitis associated with high natural concentrations of furanocoumarins in limes.
2002 Mar
Simultaneous determination of furanocoumarins in infusions and decoctions from "Carapiá" (dorstenia species) by high-performance liquid chromatography.
2002 Mar 13
3-Alkyl- and 3-aryl-7H-furo[3,2-g]-1-benzopyran-7-ones: synthesis, photoreactivity, and fluorescence properties.
2002 May
Epoxidation of some natural furocoumarins and furochromones using gamma-ray.
2002 May-Jun
Oral administration of 5-methoxypsoralen affects the distribution and metabolism of 2-aminofluorene in Sprague-Dawley rats.
2002 May-Jun
Phytochemical and pharmacological studies on Sideritis taurica Stephan ex Wild.
2002 Oct
Tea: not immoral, illegal, or fattening, but is it innocuous?
2002 Sep 14
Patents

Sample Use Guides

VITILIGO THERAPY : Two capsules (10 mg each) in one dose taken with milk or in food two to four hours before ultraviolet light exposure. PSORIASIS THERAPY: The methoxsalen capsules should be taken 2 hours before UVA exposure with some food or milk
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: 8-Methoxypsoralen was assessed for its effects on in vitro lymphocyte proliferation in the absence of ultraviolet radiation. 8-Methoxypsoralen inhibited both the phytohemagglutinin and concanavalin A-induced proliferation of normal human peripheral blood lymphocytes in a time and dose-dependent manner.
8-Methoxypsoralen inhibited both the phytohemagglutinin and concanavalin A-induced proliferation of normal human peripheral blood lymphocytes in a time and dose-dependent manner.
Name Type Language
METHOXSALEN
HSDB   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
Common Name English
VITPSO
Common Name English
METHOXSALEN [HSDB]
Common Name English
NSC-45923
Code English
XANTHOTOXIN
Common Name English
METHOXSALEN [USP MONOGRAPH]
Common Name English
SM-88 COMPONENT METHOXSALEN
Code English
8-METHOXYPSORALEN
Common Name English
OXYPSORALEN
Common Name English
METHOXSALEN [USP-RS]
Common Name English
METHOXSALEN [ORANGE BOOK]
Common Name English
METHOXSALEN [JAN]
Common Name English
Methoxsalen [WHO-DD]
Common Name English
9-Methoxy-7H-furo[3,2-g][1]benzopyran-7-one
Systematic Name English
METHOXSALEN [MART.]
Common Name English
UVADEX
Brand Name English
7H-FURO(3,2-G)(1)BENZOPYRAN-7-ONE, 9-METHOXY-
Systematic Name English
8-MOP
Brand Name English
OXSORALEN
Brand Name English
METHOXSALEN [VANDF]
Common Name English
PUVALEN
Common Name English
METHOXSALEN [IARC]
Common Name English
8-METHOXSALEN
Common Name English
METHOXSALEN [MI]
Common Name English
METOXALEN
Common Name English
Classification Tree Code System Code
NDF-RT N0000010217
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
WHO-ATC D05AD02
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WHO-ATC D05BA02
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NDF-RT N0000007909
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
EU-Orphan Drug EU/3/06/374
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
WHO-VATC QD05AD02
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
FDA ORPHAN DRUG 80594
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NCI_THESAURUS C1420
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NDF-RT N0000007909
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FDA ORPHAN DRUG 117298
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
NDF-RT N0000009801
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NCI_THESAURUS C25760
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WHO-VATC QD05BA02
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NDF-RT N0000175879
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
NDF-RT N0000007909
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
FDA ORPHAN DRUG 74293
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
LIVERTOX 620
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NDF-RT N0000175984
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
Code System Code Type Description
DRUG CENTRAL
30
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PRIMARY
MERCK INDEX
m7329
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PRIMARY Merck Index
CAS
298-81-7
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PRIMARY
HSDB
2505
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PRIMARY
MESH
D008730
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PRIMARY
RS_ITEM_NUM
1417001
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PRIMARY
SMS_ID
100000092592
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PRIMARY
RXCUI
6854
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
PRIMARY RxNorm
WIKIPEDIA
METHOXSALEN
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
PRIMARY
FDA UNII
U4VJ29L7BQ
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
PRIMARY
DRUG BANK
DB00553
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
PRIMARY
PUBCHEM
4114
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PRIMARY
CHEBI
18358
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PRIMARY
ECHA (EC/EINECS)
206-066-9
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PRIMARY
NSC
45923
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PRIMARY
NCI_THESAURUS
C643
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PRIMARY
DAILYMED
U4VJ29L7BQ
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
PRIMARY
ChEMBL
CHEMBL416
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
PRIMARY
EPA CompTox
DTXSID8020830
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
PRIMARY
LACTMED
Methoxsalen
Created by admin on Fri Dec 15 15:04:59 GMT 2023 , Edited by admin on Fri Dec 15 15:04:59 GMT 2023
PRIMARY
EVMPD
SUB14541MIG
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PRIMARY