Palovarotene

Summary

Palovarotene (CHEMBL2105648) is an approved small-molecule retinoic acid receptor γ agonist (ATC M09AX11) targeting RARG; indicated across 3 conditions including myositis ossificans and dry eye syndrome.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: M09AX11
• Targets: 1 (RARG)
• Indications: 3 conditions
• Clinical trials: 9
• Chemistry: 414.5 Da · C27H30N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2105648
Name	Palovarotene
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	10295295
ChEBI	CHEBI:188559
ATC	M09AX11
Molecular formula	C27H30N2O2
Molecular weight	414.5
InChIKey	YTFHCXIPDIHOIA-DHZHZOJOSA-N

SMILES: CC1(CCC(C2=C1C=C(C(=C2)/C=C/C3=CC=C(C=C3)C(=O)O)CN4C=CC=N4)(C)C)C

IUPAC name: 4-[(E)-2-[5,5,8,8-tetramethyl-3-(pyrazol-1-ylmethyl)-6,7-dihydronaphthalen-2-yl]ethenyl]benzoic acid

ChEBI definition: An olefinic compound that is ethene is which a hydrogen at position 1 is replaced by a 4-carboxyphenyl group and a hydrogen at position 2 is replaced by a 5,5,8,8-tetramethyl-3-[(1H-pyrazol-1-yl)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl group (the E-stereoisomer). It is a selective retinoic acid receptor γ (RARγ) agonist developed by Ipsen, to reduce the formation of new heterotopic ossification in adults and children with fibrodysplasia ossificans progressiva (FOP), a rare bone disorder.

Pharmacological roles (ChEBI): retinoic acid receptor γ agonist.

Also known as: CLM-001, IPN-60120, IPN60120, Palovarotene, Palovaroteno, R-667, RG-667, RO-3300074, RO3300074, Sohonos, PALOVAROTENE

Patent coverage: 96 distinct patent families (268 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 168 (63%) 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
RARG	Retinoic acid receptor-γ	Agonist		1.6%	P13631

Bioactivity

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

Target pathways

Aggregated over 1 target gene(s): RARG.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Nuclear Receptor transcription pathway	1	RARG
Signaling by Retinoic Acid	1	RARG
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	RARG

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	1
neural tube closure	1
glandular epithelial cell development	1
growth plate cartilage chondrocyte growth	1
apoptotic process	1
positive regulation of cell population proliferation	1
negative regulation of cell population proliferation	1
regulation of cell size	1
anterior/posterior pattern specification	1
positive regulation of gene expression	1
cell differentiation	1
embryonic camera-type eye development	1
regulation of myelination	1
negative regulation of chondrocyte differentiation	1
response to retinoic acid	1

Indications & clinical

Indications

1 approved indication. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
myositis ossificans	4	MONDO:0003964	MONDO:0007606

1 disease in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
dry eye syndrome	1	MONDO:0006733	EFO:1000906

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

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE1	4
PHASE2	3
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03312634	PHASE3	COMPLETED	An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva.
NCT05027802	PHASE3	COMPLETED	A Rollover Study to Further Evaluate the Safety and Efficacy of Palovarotene Capsules in Male and Female Participants Aged ≥14 Years With Fibrodysplasia Ossificans Progressiva (FOP) Who Have Completed the Relevant Parent Studies.
NCT02190747	PHASE2	COMPLETED	An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects
NCT02521792	PHASE2	TERMINATED	In-Home Evaluation of Episodic Administration of Palovarotene in Fibrodysplasia Ossificans Progressiva (FOP) Subjects
NCT03442985	PHASE2	TERMINATED	An Efficacy and Safety Study of Palovarotene for the Treatment of MO
NCT04762355	PHASE1	COMPLETED	Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of Palovarotene Ophthalmic Solution in Healthy Adult Subjects
NCT04829773	PHASE1	COMPLETED	Study Evaluating the Effect of Food on the Pharmacokinetics of Palovarotene and the Effect of Palovarotene on the Pharmacokinetics of the CYP3A4 Substrate Midazolam in Two Cohorts of Healthy Adult Subjects
NCT04829786	PHASE1	COMPLETED	Study to Compare the Pharmacokinetics, Safety, and Tolerability Following Administration of Palovarotene in Healthy Japanese and Non-Asian Subjects
NCT06908954	PHASE1	COMPLETED	A Study of the Blood Levels of Palovarotene in Participants With Abnormal Liver Function Compared to Healthy Adult Participants After Intake of a Single Dose

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.

35 molecules share ≥1 primary target. Top 35 by shared-target count:

Molecule	Source	Status	Shared targets
ACETAMINOPHEN	ChEMBL + PubChem	Phase 4 (approved)	RARG
ADAPALENE	ChEMBL + PubChem	Phase 4 (approved)	RARG
ALITRETINOIN	ChEMBL + PubChem	Phase 4 (approved)	RARG
ALPROSTADIL	ChEMBL + PubChem	Phase 4 (approved)	RARG
AMOXICILLIN	ChEMBL + PubChem	Phase 4 (approved)	RARG
BEXAROTENE	ChEMBL + PubChem	Phase 4 (approved)	RARG
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	RARG
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	RARG
Rosiglitazone	ChEMBL + PubChem	Phase 4 (approved)	RARG
TAZAROTENE	ChEMBL + PubChem	Phase 4 (approved)	RARG
TRETINOIN	ChEMBL + PubChem	Phase 4 (approved)	RARG
TRIFAROTENE	ChEMBL + PubChem	Phase 4 (approved)	RARG
RACECADOTRIL	ChEMBL	Phase 4 (approved)	RARG
TAMIBAROTENE	ChEMBL	Phase 4 (approved)	RARG
TROGLITAZONE	ChEMBL	Phase 4 (approved)	RARG
CONESSINE	ChEMBL	Phase 2	RARG
GLIQUIDONE	ChEMBL	Phase 2	RARG
Atorvastatin	PubChem	Approved	RARG
Bosentan	PubChem	Approved	RARG
Calcitriol	PubChem	Approved	RARG
Carprofen	PubChem	Approved	RARG
cyclosporine	PubChem	Approved	RARG
Diclofenac	PubChem	Approved	RARG
Domperidone	PubChem	Approved	RARG
ethinyl estradiol	PubChem	Approved	RARG
Pitavastatin	PubChem	Approved	RARG
Repaglinide	PubChem	Approved	RARG
rifampin	PubChem	Approved	RARG
Rivaroxaban	PubChem	Approved	RARG
Simvastatin	PubChem	Approved	RARG
Sunitinib	PubChem	Approved	RARG
Ticlopidine	PubChem	Approved	RARG
Tolcapone	PubChem	Approved	RARG
Verapamil	PubChem	Approved	RARG
Zafirlukast	PubChem	Approved	RARG