Difamilast

Summary

Difamilast (CHEMBL3989968) is a phase-3 clinical-stage small molecule targeting PDE4D; indicated across 1 condition including atopic eczema.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (PDE4D)
• Indications: 1 condition
• Clinical trials: 10
• Chemistry: 446.4 Da · C23H24F2N2O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3989968
Name	Difamilast
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	57855696
Molecular formula	C23H24F2N2O5
Molecular weight	446.4
InChIKey	VFBILHPIHUPBPZ-UHFFFAOYSA-N

SMILES: CCOC1=CC=CC=C1C(=O)NCC2=COC(=N2)C3=CC(=C(C=C3)OC(F)F)OC(C)C

IUPAC name: N-[[2-[4-(difluoromethoxy)-3-propan-2-yloxyphenyl]-1,3-oxazol-4-yl]methyl]-2-ethoxybenzamide

Also known as: Difamilast, OPA-15406, DIFAMILAST

Patent coverage: 63 distinct patent families (135 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 95 (70%) 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
PDE4D	phosphodiesterase 4D	Inhibition	7.3	0.7%	Q08499

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

Target pathways

Aggregated over 1 target gene(s): PDE4D.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
DARPP-32 events	1	PDE4D
G alpha (s) signalling events	1	PDE4D
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	PDE4D

Dominant GO biological processes

GO term	Targets
regulation of heart rate	1
cAMP catabolic process	1
positive regulation of heart rate	1
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
positive regulation of type II interferon production	1
positive regulation of interleukin-2 production	1
positive regulation of interleukin-5 production	1
negative regulation of heart contraction	1
T cell receptor signaling pathway	1
establishment of endothelial barrier	1
cellular response to cAMP	1
cellular response to epinephrine stimulus	1
adrenergic receptor signaling pathway	1
regulation of cardiac muscle cell contraction	1
negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	1

Indications & clinical

Indications

1 indication (0 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
atopic eczema	3	MONDO:0004980	EFO:0000274

Clinical trials

Total trials: 10.

Phase distribution

Phase	Trials
PHASE3	6
PHASE2	3
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07173478	PHASE3	NOT_YET_RECRUITING	A Phase 3 Trial to Demonstrate the Superiority of 1% OPA-15406 Foam to the Vehicle in Adult Patients With Atopic Dermatitis
NCT07184645	PHASE3	NOT_YET_RECRUITING	A Phase 3 Trial of OPA-15406 Foam in Children and Infants With Atopic Dermatitis
NCT03911401	PHASE3	COMPLETED	Comparison Trial of OPA-15406 Ointment in Pediatric Patients With Atopic Dermatitis
NCT05372653	PHASE3	COMPLETED	A Long-term Trial of OPA-15406 in Infants With Atopic Dermatitis
NCT05571943	PHASE3	COMPLETED	A Open-label Study to Assess the Long-term Safety of Difamilast Ointment 1% in Mild to Moderate Atopic Dermatitis
NCT05608343	PHASE3	COMPLETED	This Study is to Assess the Efficacy of Difamilast Ointment in Mild to Moderate Atopic Dermatitis(AD)
NCT02068352	PHASE2	COMPLETED	A Study to Evaluate the Effectiveness and Safety of Topical OPA-15406 Ointment to Treat Participants With Atopic Dermatitis
NCT02914548	PHASE2	COMPLETED	Study of OPA-15406 Ointment in Patients With Atopic Dermatitis
NCT03018691	PHASE2	COMPLETED	Phase 2 Study of OPA-15406 Ointment in Pediatric Patients With Atopic Dermatitis
NCT01702181	PHASE1	COMPLETED	A Safety Study to Evaluate the Use and Effectiveness of a Topical Ointment to Treat Adults With Atopic Dermatitis

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

274 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	PDE4D
TAFAMIDIS	ChEMBL + PubChem	Phase 4 (approved)	PDE4D
ABACAVIR	ChEMBL	Phase 4 (approved)	PDE4D
ABEMACICLIB	ChEMBL	Phase 4 (approved)	PDE4D
ADENOSINE	ChEMBL	Phase 4 (approved)	PDE4D
ALPIDEM	ChEMBL	Phase 4 (approved)	PDE4D
AMINOGLUTETHIMIDE	ChEMBL	Phase 4 (approved)	PDE4D
AMLEXANOX	ChEMBL	Phase 4 (approved)	PDE4D
AMOXAPINE	ChEMBL	Phase 4 (approved)	PDE4D
AMSACRINE	ChEMBL	Phase 4 (approved)	PDE4D
ANASTROZOLE	ChEMBL	Phase 4 (approved)	PDE4D
ANTAZOLINE	ChEMBL	Phase 4 (approved)	PDE4D
APOMORPHINE	ChEMBL	Phase 4 (approved)	PDE4D
APREMILAST	ChEMBL	Phase 4 (approved)	PDE4D
BELINOSTAT	ChEMBL	Phase 4 (approved)	PDE4D
BENFLUOREX	ChEMBL	Phase 4 (approved)	PDE4D
BENZBROMARONE	ChEMBL	Phase 4 (approved)	PDE4D
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	PDE4D
BUCLIZINE	ChEMBL	Phase 4 (approved)	PDE4D
BUTAMBEN	ChEMBL	Phase 4 (approved)	PDE4D
BUTOCONAZOLE	ChEMBL	Phase 4 (approved)	PDE4D
CABOZANTINIB	ChEMBL	Phase 4 (approved)	PDE4D
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	PDE4D
CARBENOXOLONE	ChEMBL	Phase 4 (approved)	PDE4D
CARPROFEN	ChEMBL	Phase 4 (approved)	PDE4D
CEFPODOXIME PROXETIL	ChEMBL	Phase 4 (approved)	PDE4D
CELECOXIB	ChEMBL	Phase 4 (approved)	PDE4D
CILOSTAZOL	ChEMBL	Phase 4 (approved)	PDE4D
CLADRIBINE	ChEMBL	Phase 4 (approved)	PDE4D
CLOBAZAM	ChEMBL	Phase 4 (approved)	PDE4D
CLOFARABINE	ChEMBL	Phase 4 (approved)	PDE4D
CLOFAZIMINE	ChEMBL	Phase 4 (approved)	PDE4D
CODEINE	ChEMBL	Phase 4 (approved)	PDE4D
CRISABOROLE	ChEMBL	Phase 4 (approved)	PDE4D
CRIZOTINIB	ChEMBL	Phase 4 (approved)	PDE4D
DACOMITINIB	ChEMBL	Phase 4 (approved)	PDE4D
DASATINIB	ChEMBL	Phase 4 (approved)	PDE4D
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	PDE4D
DESOGESTREL	ChEMBL	Phase 4 (approved)	PDE4D
DEXTROTHYROXINE	ChEMBL	Phase 4 (approved)	PDE4D
DICUMAROL	ChEMBL	Phase 4 (approved)	PDE4D
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	PDE4D
DINOPROSTONE	ChEMBL	Phase 4 (approved)	PDE4D
DIPYRIDAMOLE	ChEMBL	Phase 4 (approved)	PDE4D
DOMPERIDONE	ChEMBL	Phase 4 (approved)	PDE4D
DONEPEZIL	ChEMBL	Phase 4 (approved)	PDE4D
DOXAZOSIN	ChEMBL	Phase 4 (approved)	PDE4D
DYCLONINE	ChEMBL	Phase 4 (approved)	PDE4D
ECONAZOLE	ChEMBL	Phase 4 (approved)	PDE4D
EFAVIRENZ	ChEMBL	Phase 4 (approved)	PDE4D
ENCORAFENIB	ChEMBL	Phase 4 (approved)	PDE4D
ENOXIMONE	ChEMBL	Phase 4 (approved)	PDE4D
ENSIFENTRINE	ChEMBL	Phase 4 (approved)	PDE4D
EPALRESTAT	ChEMBL	Phase 4 (approved)	PDE4D
ERDAFITINIB	ChEMBL	Phase 4 (approved)	PDE4D
ESTAZOLAM	ChEMBL	Phase 4 (approved)	PDE4D
ETHINYL ESTRADIOL	ChEMBL	Phase 4 (approved)	PDE4D
ETORICOXIB	ChEMBL	Phase 4 (approved)	PDE4D
FEDRATINIB	ChEMBL	Phase 4 (approved)	PDE4D
FELODIPINE	ChEMBL	Phase 4 (approved)	PDE4D