Methoxsalen

Summary

Methoxsalen (CHEMBL416) is an approved small-molecule dermatologic drug (ATC D05BA02) targeting TAS2R20; indicated across 14 conditions including psoriasis and t-cell non-hodgkin lymphoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: D05BA02 (+1 more)
• Targets: 1 (TAS2R20)
• Indications: 14 conditions
• Clinical trials: 21
• Chemistry: 216.19 Da · C12H8O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL416
Name	Methoxsalen
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4114
ChEBI	CHEBI:18358
ATC	D05BA02, D05AD02
Molecular formula	C12H8O4
Molecular weight	216.19
InChIKey	QXKHYNVANLEOEG-UHFFFAOYSA-N

SMILES: COC1=C2C(=CC3=C1OC=C3)C=CC(=O)O2

IUPAC name: 9-methoxyfuro[3,2-g]chromen-7-one

ChEBI definition: A member of the class of psoralens that is 7H-furo[3,2-g]chromen-7-one in which the 9 position is substituted by a methoxy group. It is a constituent of the fruits of Ammi majus. Like other psoralens, trioxsalen causes photosensitization of the skin. It is administered topically or orally in conjunction with UV-A for phototherapy treatment of vitiligo and severe psoriasis.

Pharmacological roles (ChEBI): dermatologic drug, antineoplastic agent, photosensitizing agent.

Other ChEBI roles (chemical / environmental): cross-linking reagent, plant metabolite.

Also known as: Deltasoralen, Meladinine, Methoxsalen, METHOXSALEN COMPONENT OF SM-88, Metoxalen, NSC-45923, Oxsoralen, Oxsoralen-ultra, Oxypsoralen, Puvalen, Puvasoralen-8, Uvadex

Patent coverage: 5,547 distinct patent families (19,665 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 19,404 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
TAS2R20	TAS2R20	Agonist	4.92	0.1%	P59543

Broader ChEMBL bioactivity targets: 14 (assay-derived). Sample: Amine oxidase [flavin-containing] A, Thyrotropin receptor, Acetylcholinesterase, Sodium-dependent dopamine transporter, 3’,5’-cyclic-AMP phosphodiesterase 4A, Cytochrome P450 2D6, Tyrosinase, Cytochrome P450 1A2, Cytochrome P450 3A4, Cytochrome P450 2A13.

Bioactivity

ChEMBL activities: 22 potent at pChembl ≥ 5 of 36 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP1A2	7.8	AC50	15.85	nM	CHEMBL_ACT_6020596
CYP2A13	7.4	Ki	40	nM	CHEMBL_ACT_15468157
CYP1A2	7.4	IC50	40	nM	CHEMBL_ACT_7747351
CYP2A6	7.05	Ki	90	nM	CHEMBL_ACT_25079958
CYP2A6	6.6	Ki	250	nM	CHEMBL_ACT_15468117
CYP2A6	6.58	Ki	260	nM	CHEMBL_ACT_25079939
CYP2A6	6.34	IC50	460	nM	CHEMBL_ACT_25079944
ACHE	6.12	IC50	760	nM	CHEMBL_ACT_13371829
CYP2A6	6.1	Ki	800	nM	CHEMBL_ACT_6075000
PDE4A	5.94	AC50	1146	nM	CHEMBL_ACT_25207025
CYP2A13	5.8	Kd	1600	nM	CHEMBL_ACT_15468147
CYP2A6	5.72	Ki	1900	nM	CHEMBL_ACT_6074982
CYP2A6	5.72	Ki	1900	nM	CHEMBL_ACT_6074992
CYP3A4	5.66	Ki	2200	nM	CHEMBL_ACT_25079965
CYP2C19	5.3	Potency	5012	nM	CHEMBL_ACT_4020287
MAPK1	5.3	Potency	5012	nM	CHEMBL_ACT_4544922
CYP2D6	5.3	Potency	5012	nM	CHEMBL_ACT_4994305
CYP2C19	5.3	AC50	5012	nM	CHEMBL_ACT_6017346
CYP2D6	5.3	AC50	5012	nM	CHEMBL_ACT_6050139
CYP3A4	5.2	Potency	6310	nM	CHEMBL_ACT_4977769
CYP3A4	5.2	Potency	6310	nM	CHEMBL_ACT_5046797
CYP3A4	5.2	AC50	6310	nM	CHEMBL_ACT_6018282

Target pathways

Aggregated over 1 target gene(s): TAS2R20.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	TAS2R20
Signaling by GPCR	1	TAS2R20
GPCR downstream signalling	1	TAS2R20
G alpha (i) signalling events	1	TAS2R20
Class C/3 (Metabotropic glutamate/pheromone receptors)	1	TAS2R20
GPCR ligand binding	1	TAS2R20
Sensory Perception	1	TAS2R20
Sensory perception of taste	1	TAS2R20
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	TAS2R20

Dominant GO biological processes

GO term	Targets
detection of chemical stimulus involved in sensory perception of bitter taste	1
signal transduction	1
G protein-coupled receptor signaling pathway	1
sensory perception of taste	1

Indications & clinical

Indications

14 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
psoriasis	4	MONDO:0005083	EFO:0000676
T-cell non-Hodgkin lymphoma	4	MONDO:0015760	MONDO:0015760
lymphoma	3	MONDO:0005062	EFO:0000574
mycosis fungoides	3	MONDO:0009691	EFO:1001051
graft versus host disease	3	MONDO:0013730	EFO:0004599
Crohn disease	2	MONDO:0005011	EFO:0000384
rheumatoid arthritis	2	MONDO:0008383	EFO:0000685
acquired epidermolysis bullosa	2	MONDO:0018747	EFO:1000691
Sezary syndrome	2	MONDO:0017844	EFO:1000785
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
diffuse scleroderma	2	MONDO:0005019	EFO:0000404
lymphoid neoplasm	1	MONDO:0005157	EFO:0001642

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 21.

Phase distribution

Phase	Trials
PHASE2	14
PHASE3	2
Not specified	2
PHASE4	1
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00221039	PHASE4	COMPLETED	Photopheresis as an Interventional Therapy for the Treatment of CTCL (Cutaneous T-Cell Lymphoma, Mycosis Fungoides) Stage 1A, 1B, 2A
NCT00282503	PHASE3	TERMINATED	Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Acute Graft Versus-Host Disease
NCT02524847	PHASE3	TERMINATED	Methoxsalen and Extracorporeal Photopheresis (ECP) for the Treatment of Pediatric Participants With Steroid Refractory Acute Graft Versus Host Disease
NCT04291261	PHASE2	ACTIVE_NOT_RECRUITING	Extracorporal Photopheresis With UVADEX Plus Standard Steroid Treatment for High Risk Acute Graft-versus-host Disease
NCT04986605	PHASE2	NOT_YET_RECRUITING	Extracorporeal Photopheresis in Early Diffuse Cutaneous Systemic Sclerosis
NCT00004359	PHASE2	COMPLETED	Phase II Pilot Study of Extracorporeal Phototherapy for Epidermolysis Bullosa Acquisita
NCT00030589	PHASE2	UNKNOWN	Chemotherapy and Photodynamic Therapy in Treating Patients With Cutaneous T-Cell Lymphoma
NCT00054600	PHASE2	COMPLETED	Safety and Efficacy Study of Photopheresis With UVADEX to Prevent Graft-versus-Host Disease
NCT00054613	PHASE2	COMPLETED	Safety and Efficacy Study of Photopheresis Plus Standard Therapy to Treat Chronic Graft-versus-Host Disease
NCT00221000	PHASE2	COMPLETED	Safety and Efficacy of Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Rheumatoid Arthritis
NCT00221026	PHASE2	COMPLETED	Safety and Efficacy of Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Crohn’s Disease
NCT00639717	PHASE2	COMPLETED	Addition of Etanercept and Extracorporeal Photopheresis (ECP) to Standard Graft-Versus-Host Disease (GVHD) Prophylaxis in Stem Cell Transplant
NCT00930566	PHASE1/PHASE2	UNKNOWN	Extracorporal Photopheresis Pilot Study
NCT02322190	PHASE2	TERMINATED	Biomarkers in Acute Graft-Versus-Host Disease and Extracorporeal Photopheresis Added to Investigator Chosen Therapies of Steroid Refractory Acute GVHD
NCT03563040	PHASE2	WITHDRAWN	Study of Photopheresis in the Treatment of Erythrodermic MF and SS
NCT03605940	PHASE2	UNKNOWN	A Study Comparing Corticosteroids Alone Versus Corticosteroids and Extracorporal Photopheresis (ECP) as First-line Treatment of Standard II Acute Graft-versus-host Disease
NCT06133192	PHASE2	UNKNOWN	Steroids Versus ECP and Steroids as First-line Treatment of Grade II Acute GVHD
NCT06646016	PHASE2	WITHDRAWN	EPIC- Extracorporeal Photopheresis (ECP) for Immune-related Colitis
NCT00056355	PHASE1	COMPLETED	Extracorporeal Photopheresis to Maintain Symptoms Remission During Steroid Withdrawal in Patients With Steroid-Dependent Crohn’s Disease
NCT05157581	Not specified	RECRUITING	Extracorporeal Photopheresis in Sezary Syndrome
NCT00002011	Not specified	COMPLETED	The Therakos UVAR Photopheresis System in the Treatment of AIDS-Related Complex

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 2 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

1 molecules share ≥1 primary target. Top 1 by shared-target count:

Molecule	Source	Status	Shared targets
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	TAS2R20