Alitretinoin

Summary

Alitretinoin (CHEMBL705) is an approved small-molecule antineoplastic agent (ATC D11AH04) targeting VKORC1, RARA, and RARB; indicated across 8 conditions including neoplasm and kaposi’s sarcoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: D11AH04 (+1 more)
• Targets: 7 (VKORC1, RARA, RARB…)
• Indications: 8 conditions
• Clinical trials: 22
• Chemistry: 300.4 Da · C20H28O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL705
Name	Alitretinoin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	449171
ChEBI	CHEBI:50648
ATC	D11AH04, L01XF02
Molecular formula	C20H28O2
Molecular weight	300.4
InChIKey	SHGAZHPCJJPHSC-ZVCIMWCZSA-N

SMILES: CC1=C(C(CCC1)(C)C)/C=C/C(=C\C=C\C(=C\C(=O)O)\C)/C

IUPAC name: (2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid

ChEBI definition: A retinoic acid in which the exocyclic double bonds have 7E,9Z,11E,13E geometry.

Pharmacological roles (ChEBI): antineoplastic agent, retinoid X receptor agonist, keratolytic drug.

Other ChEBI roles (chemical / environmental): metabolite.

Also known as: AGN 192013, AGN-192013, AGN192013, Alitretinoin, Alitretinoina, Alitretinoine, ALRT-1057, ALRT1057, BAL-4079, LG-100057, LG100057, LGD-1057

Patent coverage: 10,446 distinct patent families (39,246 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
VKORC1	vitamin K epoxide reductase complex subunit 1	Inhibition		0%	Q9BQB6
RARA	Retinoic acid receptor-α	Agonist	9.5	0.8%	P10276
RARB	Retinoic acid receptor-β	Agonist	9.7	0.1%	P10826
RARG	Retinoic acid receptor-γ	Agonist	9	1.6%	P13631
RXRA	Retinoid X receptor-α	Agonist	8.2	5.1%	P19793
RXRB	Retinoid X receptor-β	Agonist	8.2	0.2%	P28702
RXRG	Retinoid X receptor-γ	Agonist	8	0.2%	P48443

Broader ChEMBL bioactivity targets: 23 (assay-derived). Sample: Microtubule-associated protein tau, Nuclear receptor subfamily 4immunitygroup A member 1, Nuclear receptor ROR-gamma, Ferritin light chain, Nuclear receptor ROR-gamma, Retinoic acid receptor RXR-beta, Retinoic acid receptor gamma, Retinoic acid receptor RXR-gamma, Retinoic acid receptor beta, Retinoic acid receptor alpha.

Bioactivity

ChEMBL activities: 151 potent at pChembl ≥ 5 of 161 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
RARB	9.3	Ki	0.5	nM	CHEMBL_ACT_221433
RARB	9.15	Ki	0.7	nM	CHEMBL_ACT_221432
RARG	9.1	Kd	0.8	nM	CHEMBL_ACT_1612378
RARB	9.1	EC50	0.8	nM	CHEMBL_ACT_24858588
RARA	9	EC50	1	nM	CHEMBL_ACT_24858587
RARG	9	Ki	1	nM	CHEMBL_ACT_657659
RXRA	8.82	Kd	1.5	nM	CHEMBL_ACT_1612377
RXRA	8.82	EC50	1.5	nM	CHEMBL_ACT_818769
RARB	8.7	AC50	2	nM	CHEMBL_ACT_381132
RXRB	8.59	EC50	2.6	nM	CHEMBL_ACT_239998
RXRA	8.52	Kd	3	nM	CHEMBL_ACT_372911
RARG	8.52	AC50	3	nM	CHEMBL_ACT_381133
RARB	8.52	EC50	3	nM	CHEMBL_ACT_818767
RARB	8.48	EC50	3.3	nM	CHEMBL_ACT_268016
RARB	8.48	EC50	3.3	nM	CHEMBL_ACT_317600
RARB	8.48	EC50	3.3	nM	CHEMBL_ACT_476554
RXRB	8.42	Ki	3.8	nM	CHEMBL_ACT_657661
RXRA	8.4	EC50	4	nM	CHEMBL_ACT_22450482
RXRG	8.4	IC50	4	nM	CHEMBL_ACT_658378
RARG	8.4	EC50	4	nM	CHEMBL_ACT_818768
P28705	8.4	Kd	4	nM	CHEMBL_ACT_993460
RXRG	8.37	EC50	4.3	nM	CHEMBL_ACT_240000
RXRG	8.35	EC50	4.5	nM	CHEMBL_ACT_818771
RXRA	8.22	EC50	6	nM	CHEMBL_ACT_239994
RXRA	8.22	EC50	6	nM	CHEMBL_ACT_24858589
RXRB	8.22	EC50	6	nM	CHEMBL_ACT_24858590
RARG	8.22	EC50	6	nM	CHEMBL_ACT_268017
RARG	8.22	EC50	6	nM	CHEMBL_ACT_317601
RARG	8.22	EC50	6	nM	CHEMBL_ACT_476555
RXRA	8.15	AC50	7	nM	CHEMBL_ACT_381134

Target pathways

Aggregated over 7 target gene(s): VKORC1, RARA, RARB, RARG, RXRA, RXRB, RXRG.

Top Reactome pathways

67 total, by targets touching each:

Pathway	Targets	Genes
Nuclear Receptor transcription pathway	6	RARA, RARB, RARG, RXRA, RXRB, RXRG
Signaling by Retinoic Acid	6	RARA, RARB, RARG, RXRA, RXRB, RXRG
Activation of anterior HOX genes in hindbrain development during early embryogenesis	4	RARA, RARB, RARG, RXRA
Signal Transduction	3	RXRA, RXRB, RXRG
Generic Transcription Pathway	3	RXRA, RXRB, RXRG
RNA Polymerase II Transcription	3	RXRA, RXRB, RXRG
Gene expression (Transcription)	3	RXRA, RXRB, RXRG
Signaling by Nuclear Receptors	3	RXRA, RXRB, RXRG
Metabolism	2	RXRA, RXRB
PPARA activates gene expression	2	RXRA, RXRB
Regulation of lipid metabolism by PPARalpha	2	RXRA, RXRB
SUMOylation of intracellular receptors	2	RARA, RXRA
Metabolism of lipids	2	RXRA, RXRB
NR1H2 and NR1H3-mediated signaling	2	RXRA, RXRB
NR1H2 & NR1H3 regulate gene expression linked to lipogenesis	2	RXRA, RXRB
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	2	RXRA, RXRB
NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake	2	RXRA, RXRB
NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose	2	RXRA, RXRB
Transcriptional regulation of granulopoiesis	2	RARA, RXRA
NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis	2	RXRA, RXRB
NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis	2	RXRA, RXRB
TGFBR3 expression	2	RARA, RXRA
Developmental Biology	1	RXRA
R-HSA-1368082	1	RXRA
BMAL1:CLOCK,NPAS2 activates circadian expression	1	RXRA
Mitochondrial biogenesis	1	RXRA
Recycling of bile acids and salts	1	RXRA
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	RXRA
Organelle biogenesis and maintenance	1	RXRA
Synthesis of bile acids and bile salts	1	RXRA

Dominant GO biological processes

GO term	Targets
cell differentiation	6
positive regulation of transcription by RNA polymerase II	6
retinoic acid receptor signaling pathway	6
regulation of DNA-templated transcription	6
bone development	4
negative regulation of transcription by RNA polymerase II	4
glandular epithelial cell development	3
growth plate cartilage development	3
regulation of myelination	3
response to retinoic acid	3
multicellular organism growth	3
mRNA transcription by RNA polymerase II	3
positive regulation of DNA-templated transcription	3
ventricular cardiac muscle cell differentiation	3
negative regulation of cartilage development	3

Indications & clinical

Indications

8 indications (3 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
neoplasm	4	MONDO:0005070	EFO:0000616
Kaposi’s sarcoma	4	MONDO:0005055	EFO:0000558
hand dermatosis	3	MONDO:0006556	EFO:1000706
psoriasis	2	MONDO:0005083	EFO:0000676
cutaneous lupus erythematosus	2	MONDO:0005282	EFO:0003834
lichen planus	2	MONDO:0006572	EFO:1000726
breast neoplasm	1	MONDO:0021100	MONDO:0007254

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

Clinical trials

Total trials: 22.

Phase distribution

Phase	Trials
PHASE3	9
PHASE2	8
Not specified	2
PHASE4	1
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01231854	PHASE4	TERMINATED	Ciclosporin Versus Alitretinoin for Severe Atopic Hand Dermatitis.
NCT00124436	PHASE3	COMPLETED	Follow-up Efficacy and Safety of Alitretinoin in Severe Chronic Hand Dermatitis
NCT00124475	PHASE3	COMPLETED	Efficacy and Safety of a Retinoid for the Treatment of Severe Chronic Hand Dermatitis
NCT00309621	PHASE3	COMPLETED	Safety and Efficacy of a Retinoid for the Treatment of Severe Chronic Hand Dermatitis
NCT00519675	PHASE3	COMPLETED	Alitretinoin in the Treatment of Chronic Hand Eczema
NCT00817063	PHASE3	COMPLETED	Efficacy and Safety of a Retinoid in the Treatment of Severe Chronic Hand Eczema
NCT03026907	PHASE3	UNKNOWN	Alitretinoin vs Azathioprine in Severe Non-hyperkeratotic Hand Eczema
NCT03026946	PHASE3	UNKNOWN	Alitretinoin vs Cyclosporine in Severe Recurrent Vesicular Hand Eczema
NCT03370367	PHASE3	COMPLETED	Double Blind Phase III Trial of Effects of Low Dose 13-Cisretinoic Acid on Prevention of Second Primaries in Stages I-II Head and Neck Cancer
NCT05259722	PHASE3	COMPLETED	A 24 Week Trial to Compare the Efficacy and Safety of Delgocitinib Cream 20 mg/g Twice-daily With Alitretinoin Capsules Once-daily in Adult Participants With Severe Chronic Hand Eczema
NCT00002188	PHASE2	COMPLETED	A Study of ALRT1057 in Patients With AIDS-Related Kaposi’s Sarcoma
NCT00002586	PHASE2	COMPLETED	13-Cis Retinoic Acid With or Without Vitamin E for Prevention of Lung Cancer
NCT00135135	PHASE2	COMPLETED	Therapy for Children With Neuroblastoma
NCT01245140	PHASE2	COMPLETED	Efficacy of Alitretinoin Treatment in Patients With Pustular Form of Psoriasis
NCT01261923	PHASE1/PHASE2	COMPLETED	Pharmacokinetics of 9-cis-retinoic Acid (Alitretinoin, Toctino®) in Patients With Hepatic Disease
NCT01407679	PHASE2	TERMINATED	Efficacy and Safety of Oral Alitretinoin (Toctino®) in the Treatment of Patients With Cutaneous Lupus Erythematosus
NCT01538732	PHASE2	UNKNOWN	Lichen Planus Mucosae at USZ, Efficacy of Oral Alitretinoin
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT03323801	PHASE2	COMPLETED	RA-4: 13-cis Retinoic Acid for Treatment of Men With Azoospermia
NCT00001504	PHASE1	COMPLETED	A Phase I Trial of Tamoxifen and 9-Cis-Retinoic Acid in Breast Cancer Patients
NCT00002439	Not specified	COMPLETED	A Study of ALRT 1057 Topical Gel in Patients With AIDS-Related Kaposi’s Sarcoma
NCT01891526	Not specified	COMPLETED	Single Dose of 9-cis-retinoic Acid in Hepatic Patients

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.

56 molecules share ≥1 primary target. Top 56 by shared-target count:

Molecule	Source	Status	Shared targets
BEXAROTENE	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG, RXRA, RXRB, RXRG
Calcitriol	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG, RXRA, RXRB, RXRG
TRETINOIN	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG, RXRA, RXRB, RXRG
Rosiglitazone	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG, RXRA
Acetaminophen	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
ADAPALENE	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
cyclosporine	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Olanzapine	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
OXAPROZIN	ChEMBL + PubChem	Phase 4 (approved)	RXRA, RXRB, RXRG
REGORAFENIB	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
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
IRX-4204	ChEMBL	Phase 2	RXRA, RXRB, RXRG
PIRINIXIC ACID	ChEMBL	Phase 2	RXRA, RXRB, RXRG
Atorvastatin	PubChem	Approved	RARA, RARB, RARG
Bosentan	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
Domperidone	ChEMBL + PubChem	Phase 4 (approved)	RARG, RXRA
Pitavastatin	ChEMBL + PubChem	Phase 4 (approved)	RARG, RXRA
TROGLITAZONE	ChEMBL	Phase 4 (approved)	RARB, RARG
Rivaroxaban	PubChem	Approved	RARB, RARG
SULINDAC	ChEMBL + PubChem	Phase 4 (approved)	RXRA
WARFARIN	ChEMBL + PubChem	Phase 4 (approved)	VKORC1
FLUVASTATIN	ChEMBL	Phase 4 (approved)	RXRA
IBUPROFEN	ChEMBL	Phase 4 (approved)	RARB
KETOCONAZOLE	ChEMBL	Phase 4 (approved)	RARB
LEVOTHYROXINE	ChEMBL	Phase 4 (approved)	RXRA
MECLOFENAMIC ACID	ChEMBL	Phase 4 (approved)	RXRA
PIOGLITAZONE	ChEMBL	Phase 4 (approved)	RXRA
RACECADOTRIL	ChEMBL	Phase 4 (approved)	RARG
TROVAFLOXACIN	ChEMBL	Phase 4 (approved)	RARB
DOCONEXENT	ChEMBL	Phase 3	RXRA
ICOSAPENT	ChEMBL	Phase 3	RXRA
TIRATRICOL	ChEMBL	Phase 3	RXRA
MOLIBRESIB	ChEMBL	Phase 2	RARA
NRX195183	ChEMBL	Phase 2	RARA
arsenic trichloride	PubChem	Approved	RARA
arsenic triiodide	PubChem	Approved	RARA
Berberine Chloride	PubChem	Approved	RXRA
Ezetimibe	PubChem	Approved	RXRA
Retinol	PubChem	Approved	RARA