Adapalene

Summary

Adapalene (CHEMBL1265) is an approved small-molecule dermatologic drug (ATC D10AD53) targeting RARA, RARB, and RARG; indicated across 3 conditions including acne and molluscum contagiosum.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: D10AD53 (+1 more)
• Targets: 3 (RARA, RARB, RARG)
• Indications: 3 conditions
• Clinical trials: 49
• Chemistry: 412.5 Da · C28H28O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1265
Name	Adapalene
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	60164
ChEBI	CHEBI:31174
ATC	D10AD53, D10AD03
Molecular formula	C28H28O3
Molecular weight	412.5
InChIKey	LZCDAPDGXCYOEH-UHFFFAOYSA-N

SMILES: COC1=C(C=C(C=C1)C2=CC3=C(C=C2)C=C(C=C3)C(=O)O)C45CC6CC(C4)CC(C6)C5

IUPAC name: 6-[3-(1-adamantyl)-4-methoxyphenyl]naphthalene-2-carboxylic acid

ChEBI definition: A naphthoic acid that is CD437 in which the phenolic hydroxy group has been converted to its methyl ether.

Pharmacological roles (ChEBI): dermatologic drug, non-steroidal anti-inflammatory drug, EC 2.7.11.22 (cyclin-dependent kinase) inhibitor.

Also known as: Adapalene, Adapalene component of cabtreo, Adapalene component of epiduo, Adapalene component of idp-126, Adapaleno, CD 271, CD-271, Differin, SID26758039, ADAPALENE, adapalene, SID174006867

Patent coverage: 3,489 distinct patent families (12,179 SureChEMBL compound mentions), from 5 matched compound structure(s). One matched structure accounts for 12,013 (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
RARA	Retinoic acid receptor-α	Agonist	5.96	0.8%	P10276
RARB	Retinoic acid receptor-β	Agonist	7.47	0.1%	P10826
RARG	Retinoic acid receptor-γ	Agonist	6.89	1.6%	P13631

Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Nuclear receptor ROR-gamma, Prelamin-A/C, RecQ-like DNA helicase BLM, Retinoic acid receptor gamma, Retinoic acid receptor beta, Retinoic acid receptor alpha, Progesterone receptor, Menin/Histone-lysine N-methyltransferase MLL, Aspartate aminotransferase, cytoplasmic.

Bioactivity

ChEMBL activities: 18 potent at pChembl ≥ 5 of 24 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
RARB	8.7	EC50	2	nM	CHEMBL_ACT_18529184
RARB	8.7	EC50	2	nM	CHEMBL_ACT_26335880
RARG	8.52	EC50	3	nM	CHEMBL_ACT_26335881
RARG	8.51	EC50	3.1	nM	CHEMBL_ACT_18529105
RARA	7.66	EC50	22	nM	CHEMBL_ACT_18529137
RARA	7.66	EC50	22	nM	CHEMBL_ACT_26335879
RARB	7.47	Ki	34	nM	CHEMBL_ACT_145035
RARB	7.47	Ki	34	nM	CHEMBL_ACT_430662
RARG	6.89	Ki	130	nM	CHEMBL_ACT_145036
RARG	6.89	Ki	130	nM	CHEMBL_ACT_430663
RARA	5.96	Ki	1100	nM	CHEMBL_ACT_145034
RARA	5.96	Ki	1100	nM	CHEMBL_ACT_430661
GLRA1	5.89	EC50	1300	nM	CHEMBL_ACT_15241389
P22002	5.82	AC50	1500	nM	CHEMBL_ACT_25119715
HSPD1	5.64	IC50	2300	nM	CHEMBL_ACT_19209373
LMNA	5.5	Potency	3162	nM	CHEMBL_ACT_3660330
PGR	5.38	AC50	4200	nM	CHEMBL_ACT_25222239
P15207	5.07	AC50	8500	nM	CHEMBL_ACT_25232388

Target pathways

Aggregated over 3 target gene(s): RARA, RARB, RARG.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Nuclear Receptor transcription pathway	3	RARA, RARB, RARG
Signaling by Retinoic Acid	3	RARA, RARB, RARG
Activation of anterior HOX genes in hindbrain development during early embryogenesis	3	RARA, RARB, RARG
SUMOylation of intracellular receptors	1	RARA
Transcriptional regulation of granulopoiesis	1	RARA
TGFBR3 expression	1	RARA

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	3
glandular epithelial cell development	3
growth plate cartilage development	3
cell differentiation	3
regulation of myelination	3
multicellular organism growth	3
positive regulation of transcription by RNA polymerase II	3
retinoic acid receptor signaling pathway	3
negative regulation of cartilage development	3
regulation of DNA-templated transcription	3
bone development	3
ureteric bud development	2
neural tube closure	2
outflow tract septum morphogenesis	2
positive regulation of cell population proliferation	2

Indications & clinical

Indications

3 indications (1 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
acne	4	MONDO:0011438	EFO:0003894
molluscum contagiosum	3	MONDO:0005855	EFO:0007375
skin disorder	1	MONDO:0005093	EFO:0000701

Clinical trials

Total trials: 49.

Phase distribution

Phase	Trials
PHASE4	20
PHASE3	14
Not specified	6
PHASE1	4
PHASE2	3
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07524946	PHASE4	NOT_YET_RECRUITING	Study to Assess Safety, Pharmacokinetics, and Treatment Effect of Cabtreo
NCT00660985	PHASE4	COMPLETED	Pharmacokinetic Study to Compare the Systemic Exposure of Differin® Gel, 0.3% or Differin® Gel, 0.1%
NCT00696449	PHASE4	COMPLETED	Analysis of Adherence in Subjects Undergoing Differin Gel, 0.1% Treatment of Moderate to Severe Acne Vulgaris
NCT00829049	PHASE4	TERMINATED	Safety and Efficacy of Tazarotene Cream 0.1% Compared With Adapalene Gel 0.3% in the Treatment of Moderate to Severe Facial Acne Vulgaris
NCT00887484	PHASE4	COMPLETED	A Comparative Study of the Tolerability of Two Combination Therapies for the Treatment of Acne
NCT00907101	PHASE4	COMPLETED	Evaluate Effectiveness of Epiduo® Gel in Reducing Antibiotic Sensitive & Resistant Strains of Propionibacterium (P)Acnes
NCT00919191	PHASE4	COMPLETED	Evaluation of Irritation by Two Facial Gels Applied to Opposite Sides of the Face
NCT00952523	PHASE4	COMPLETED	Evaluation of Irritation That Potentially Could be Caused by Two Facial Gels Applied to Opposite Sides of the Face
NCT01138735	PHASE4	COMPLETED	Epiduo Pediatric Acne Study
NCT01209949	PHASE4	COMPLETED	Assessment of Subjects’ Efficacy and Experiences Using Adapalene BPO Gel in the Treatment of Acne Vulgaris
NCT01387048	PHASE4	COMPLETED	Study for Long-term Treatment of Acne Vulgaris With Skinoren Versus Differin
NCT01504204	PHASE4	COMPLETED	Effect of Samples on Acne Treatment With Epiduo® Gel
NCT01951417	PHASE4	COMPLETED	Adapalene BPO Gel Pump, Moisturizer SPF 30 and Foam Wash in Patients With Mild to Moderate Acne Vulgaris
NCT02249104	PHASE4	COMPLETED	A Treatment Regimen for Student Athletes With Mild to Moderate Acne Vulgaris
NCT02721173	PHASE4	COMPLETED	Tazarotene Plus Clindamycin vs. Adapalene Plus Clindamycin in the Treatment of Facial Acne Vulgaris
NCT02899000	PHASE4	COMPLETED	A Treatment for Severe Inflammatory Acne Subjects
NCT03457636	PHASE4	COMPLETED	The Use of Oracea and Epiduo Forte in Severe Acne Patients
NCT03626298	PHASE4	COMPLETED	Efficacy and Tolerability of Nicotinamide Plus Cream for Moderate Acne Vulgaris in Indonesia
NCT03866447	PHASE4	UNKNOWN	Role of Vitamin D and Its Topical Analogues in Pathogenesis and Treatment of Acne Vulgaris
NCT06336603	PHASE4	COMPLETED	A Study Assessing the Efficacy of Combined Use of Clascoterone 1% Cream and Adapalene 0.3% for the Treatment of Acne
NCT06775314	PHASE3	NOT_YET_RECRUITING	The Effectiveness and Safety of Cleanser Containing Triethyl Citrate, Pyruvic Acid, Combination Cream Containing Triethyl Citrate, Ethyl Linoleate, GT Peptide-10, Salicylic Acid 0,5%, Zinc Lactate, Hyaluronic Acid and Spot Cream Containing Triethyl Citrate, Ethyl Linoleate, GT Peptide-10, Honokiol
NCT00421993	PHASE3	COMPLETED	A Study to Demonstrate the Efficacy and Safety of Adapalene/Benzoyl Peroxide Topical Gel in Subjects With Acne Vulgaris
NCT00422240	PHASE3	COMPLETED	Study to Demonstrate the Efficacy and Safety of Adapalene/Benzoyl Peroxide Topical Gel in Subjects With Acne Vulgaris
NCT00446043	PHASE3	COMPLETED	Long-term Study of Efficacy/Safety of Adapalene/Benzoyl Peroxide Topical Gel in Acne Vulgaris Subjects
NCT00687908	PHASE3	COMPLETED	Adapalene-Benzoy Peroxide (BPO) Gel in the Treatment of Acne Vulgaris as a 6-month Maintenance
NCT01014689	PHASE3	COMPLETED	Comparison of Epiduo Associated With Lymecycline Versus Epiduo Vehicle Associated With Lymecycline in Acne Vulgaris
NCT01406080	PHASE3	COMPLETED	A Comparative Study of Adapalene Gel,0.3% Versus Tretinoin Emollient Cream, 0.05% for the Treatment of Photoaging
NCT02525549	PHASE3	COMPLETED	Comparative Safety and Bioequivalence of Two Treatments in the Treatment of Acne Vulgaris
NCT02651220	PHASE3	COMPLETED	Clinical End Point Study of Generic Adapalene and Benzoyl Peroxide Gel Versus Epiduo® Forte Gel in Treatment of Acne Vulgaris
NCT02716090	PHASE3	WITHDRAWN	Clinical Trial Phase III to Assess the Non-inferiority of Dalap Duo® Product Compared to Epiduo® in the Treatment of Acne Vulgaris
NCT02932267	PHASE3	COMPLETED	Subject Reported Outcomes With Use of Adapalene 0.3% - Benzoyl Peroxide (BPO) 2.5% in Dark Skin Acne
NCT03393494	PHASE3	COMPLETED	Bioequivalence Study of Two Treatments in the Treatment of Acne Vulgaris on the Face
NCT03650361	PHASE3	COMPLETED	Bioequivalence Study of Adapalene Gel 0.3% in Subjects With Facial Acne Vulgaris
NCT04329403	PHASE3	WITHDRAWN	Clinical Endpoint Bioequivalence Study of Adapalene Gel 0.1%
NCT07473895	PHASE2	NOT_YET_RECRUITING	Topical 5% Spironolactone Gel Versus 0.1% Adapalene Gel for Acne Vulgaris: A Randomized Split-Face Study
NCT01213199	PHASE2	COMPLETED	Adapalene Gel 0.3% in the Treatment of Atrophic Acne Scars
NCT02593383	PHASE1/PHASE2	COMPLETED	Compound Adapalene and Clindamycin Hydrochloride Gel in Treatment of Patients With Acne
NCT05899699	PHASE2	UNKNOWN	Effect of New Topical Preparation for Treatment of Acne Vulgaris
NCT01182636	PHASE1	COMPLETED	Bioequivalence of Adapalene Topical Gel in Patients With Acne Vulgaris
NCT01425320	PHASE1	WITHDRAWN	Pharmacokinetics Study of Dapsone-Adapalene Fixed Combination Gel in Acne

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

42 molecules share ≥1 primary target. Top 42 by shared-target count:

Molecule	Source	Status	Shared targets
Acetaminophen	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
ALITRETINOIN	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Alprostadil	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Amoxicillin	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
BEXAROTENE	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
cyclosporine	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Olanzapine	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Rosiglitazone	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
TAZAROTENE	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Tolcapone	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
TRETINOIN	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
TRIFAROTENE	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Zafirlukast	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
TAMIBAROTENE	ChEMBL	Phase 4 (approved)	RARA, RARB, RARG
CONESSINE	ChEMBL	Phase 2	RARA, RARB, RARG
GLIQUIDONE	ChEMBL	Phase 2	RARA, RARB, RARG
Atorvastatin	PubChem	Approved	RARA, RARB, RARG
Bosentan	PubChem	Approved	RARA, RARB, RARG
Calcitriol	PubChem	Approved	RARA, RARB, RARG
Carprofen	PubChem	Approved	RARA, RARB, RARG
Diclofenac	PubChem	Approved	RARA, RARB, RARG
ethinyl estradiol	PubChem	Approved	RARA, RARB, RARG
Repaglinide	PubChem	Approved	RARA, RARB, RARG
rifampin	PubChem	Approved	RARA, RARB, RARG
Simvastatin	PubChem	Approved	RARA, RARB, RARG
Sunitinib	PubChem	Approved	RARA, RARB, RARG
Ticlopidine	PubChem	Approved	RARA, RARB, RARG
Verapamil	PubChem	Approved	RARA, RARB, RARG
TROGLITAZONE	ChEMBL	Phase 4 (approved)	RARB, RARG
Rivaroxaban	PubChem	Approved	RARB, RARG
IBUPROFEN	ChEMBL	Phase 4 (approved)	RARB
KETOCONAZOLE	ChEMBL	Phase 4 (approved)	RARB
RACECADOTRIL	ChEMBL	Phase 4 (approved)	RARG
TROVAFLOXACIN	ChEMBL	Phase 4 (approved)	RARB
MOLIBRESIB	ChEMBL	Phase 2	RARA
NRX195183	ChEMBL	Phase 2	RARA
arsenic trichloride	PubChem	Approved	RARA
arsenic triiodide	PubChem	Approved	RARA
Domperidone	PubChem	Approved	RARG
Pitavastatin	PubChem	Approved	RARG
Retinol	PubChem	Approved	RARA