Trifarotene

Summary

Trifarotene (CHEMBL3707313) is an approved small molecule (ATC D10AD06) targeting RARA, RARB, and RARG; indicated across 3 conditions including acne and autosomal recessive congenital ichthyosis 1.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: D10AD06
• Targets: 3 (RARA, RARB, RARG)
• Indications: 3 conditions
• Clinical trials: 9
• Chemistry: 459.6 Da · C29H33NO4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3707313
Name	Trifarotene
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	11518241
ATC	D10AD06
Molecular formula	C29H33NO4
Molecular weight	459.6
InChIKey	MFBCDACCJCDGBA-UHFFFAOYSA-N

SMILES: CC(C)(C)C1=C(C=CC(=C1)C2=C(C=CC(=C2)C3=CC=C(C=C3)C(=O)O)OCCO)N4CCCC4

IUPAC name: 4-[3-(3-tert-butyl-4-pyrrolidin-1-ylphenyl)-4-(2-hydroxyethoxy)phenyl]benzoic acid

Also known as: Aklief, CD-5789, CD5789, Trifarotene, Trifaroteno, TRIFAROTENE

Patent coverage: 107 distinct patent families (224 SureChEMBL compound mentions), from 1 matched compound structure(s). 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	6.3	0.8%	P10276
RARB	Retinoic acid receptor-β	Agonist	6.9	0.1%	P10826
RARG	Retinoic acid receptor-γ	Agonist	8.11	1.6%	P13631

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Retinoic acid receptor gamma, Retinoic acid receptor beta, Retinoic acid receptor alpha.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
RARG	8.7	Kd	2	nM	CHEMBL_ACT_16880275
RARG	8.11	EC50	7.7	nM	CHEMBL_ACT_18529133
RARB	7.82	Kd	15	nM	CHEMBL_ACT_16880257
RARB	6.9	EC50	125	nM	CHEMBL_ACT_18529203
RARA	6.3	Kd	500	nM	CHEMBL_ACT_16880238
RARA	6.3	EC50	500	nM	CHEMBL_ACT_18529158

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
autosomal recessive congenital ichthyosis 1	2	MONDO:0009441	MONDO:0017778
lymphoma	1	MONDO:0005062	EFO:0000574

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE3	4
PHASE4	3
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04451330	PHASE4	COMPLETED	A Study to Compare Efficacy and Safety of Trifarotene Cream When Used With an Oral Antibiotic for the Treatment of Severe Acne Vulgaris (AV)
NCT04856904	PHASE4	COMPLETED	Study of Trifarotene Cream to Assess Risk of a Trophic Acne Scar Formation
NCT05089708	PHASE4	COMPLETED	AkLief Evaluation in Acne-induced Post-Inflammatory Hyperpigmentation
NCT07186413	PHASE3	RECRUITING	A Study to Compare the Efficacy, Safety and Pharmacokinetics of Trifarotene 50 mcg/g Cream in Chinese Subjects With Acne Vulgaris
NCT02189629	PHASE3	COMPLETED	CD5789 (Trifarotene) Long Term Safety Study on Acne Vulgaris
NCT03915860	PHASE3	COMPLETED	Participant Reported Outcomes With Use of Trifarotene 50 μg/g Cream in the Treatment of Moderate Facial and Truncal Acne Vulgaris
NCT05550337	PHASE3	COMPLETED	Study Comparing Trifarotene Cream, 0.005% To AKLIEF ® (Trifarotene 0.005% Cream) In The Treatment Of Acne Vulgaris
NCT01616654	PHASE2	COMPLETED	Dose Range Study of CD5789 in Acne Vulgaris
NCT01804335	PHASE1	COMPLETED	CD5789 in Early Cutaneous T-Cell Lymphoma (CTCL)

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.

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
ADAPALENE	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
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