Rolapitant

Summary

Rolapitant (CHEMBL3707331) is an approved small-molecule neurokinin-1 receptor antagonist (ATC A04AD14) targeting TACR1; indicated across 3 conditions.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A04AD14
• Targets: 1 (TACR1)
• Indications: 3 conditions
• Clinical trials: 8
• Chemistry: 500.5 Da · C25H26F6N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3707331
Name	Rolapitant
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	10311306
ChEBI	CHEBI:90908
ATC	A04AD14
Molecular formula	C25H26F6N2O2
Molecular weight	500.5
InChIKey	FIVSJYGQAIEMOC-ZGNKEGEESA-N

SMILES: C[C@H](C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OC[C@]2(CC[C@]3(CCC(=O)N3)CN2)C4=CC=CC=C4

IUPAC name: (5S,8S)-8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-1,9-diazaspiro[4.5]decan-2-one

ChEBI definition: An azaspiro compound that is 1,7-diazaspiro[4.5]decan-2-one carrying additional phenyl and 1-{[3,5-bis(trifluoromethyl)phenyl]ethoxy}methyl substituents at position 8. Used (in the form of the hydrochloride hydrate) for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy.

Pharmacological roles (ChEBI): antiemetic, neurokinin-1 receptor antagonist.

Also known as: Rolapitant, Varuby, ROLAPITANT, rolapitant

Parent form; salt/anhydrous children: CHEMBL3707330

Patent coverage: 411 distinct patent families (980 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
TACR1	NK1 receptor	Antagonist	9.18	0.7%	P25103

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Substance-P receptor.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
TACR1	9.18	Ki	0.66	nM	CHEMBL_ACT_16885575

Target pathways

Aggregated over 1 target gene(s): TACR1.

Top Reactome pathways

4 total, by targets touching each:

Pathway	Targets	Genes
Tachykinin receptors bind tachykinins	1	TACR1
G alpha (q) signalling events	1	TACR1
Cargo recognition for clathrin-mediated endocytosis	1	TACR1
Clathrin-mediated endocytosis	1	TACR1

Dominant GO biological processes

GO term	Targets
aggressive behavior	1
positive regulation of leukocyte migration	1
angiotensin-mediated drinking behavior	1
inflammatory response	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
positive regulation of cytosolic calcium ion concentration	1
phospholipase C-activating tachykinin receptor signaling pathway	1
tachykinin receptor signaling pathway	1
long-term memory	1
associative learning	1
detection of abiotic stimulus	1
response to ozone	1
positive regulation of epithelial cell migration	1
response to auditory stimulus	1

Indications & clinical

Indications

3 indications (0 at ChEMBL trial phase 4).

The 3 indication records carry no mapped disease name (EFO/MeSH-only); none shown.

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE3	3
PHASE2	2
PHASE1	2
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01499849	PHASE3	COMPLETED	Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy
NCT01500213	PHASE3	COMPLETED	Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy
NCT01500226	PHASE3	COMPLETED	Ph 3 Safety/Efficacy Study of Rolapitant for Prevention of CINV in Subjects Receiving Moderately Emetogenic Chemotherapy
NCT02991456	PHASE2	COMPLETED	Rolapitant as an Antiemetic in Malignant Glioma Patients Receiving Radiotherapy and Temozolomide
NCT03960151	PHASE2	WITHDRAWN	Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy
NCT02382666	PHASE1	COMPLETED	A Phase 1, 2-Part, Single Ascending Dose Assessment of the Safety, Tolerability, and Pharmacokinetics of Rolapitant Intravenous in Healthy Volunteers
NCT02434861	PHASE1	COMPLETED	An Open Label, Single Dose, Three Part Study to Assess the Effects of Rolapitant (2 mg/mL IV Solution) on the Pharmacokinetics of Digoxin; Sulfasalazine; and the Cooperstown Cocktail (Midazolam, Omeprazole, Warfarin, Caffeine, and Dextromethorphan in Healthy Subjects
NCT07442890	Not specified	NOT_YET_RECRUITING	A Cohort Study on the Prevention of Nausea and Vomiting Induced by Concurrent Chemoradiotherapy for Lung Cancer Using Rolapitant and Palonosetron

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.

44 molecules share ≥1 primary target. Top 44 by shared-target count:

Molecule	Source	Status	Shared targets
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	TACR1
FIDAXOMICIN	ChEMBL + PubChem	Phase 4 (approved)	TACR1
AMOXAPINE	ChEMBL	Phase 4 (approved)	TACR1
APREPITANT	ChEMBL	Phase 4 (approved)	TACR1
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	TACR1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	TACR1
BOSUTINIB	ChEMBL	Phase 4 (approved)	TACR1
CARVEDILOL	ChEMBL	Phase 4 (approved)	TACR1
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	TACR1
CYCLOSPORINE	ChEMBL	Phase 4 (approved)	TACR1
DEXTROMETHORPHAN	ChEMBL	Phase 4 (approved)	TACR1
DOXAZOSIN	ChEMBL	Phase 4 (approved)	TACR1
ECONAZOLE	ChEMBL	Phase 4 (approved)	TACR1
HALOPERIDOL	ChEMBL	Phase 4 (approved)	TACR1
ITRACONAZOLE	ChEMBL	Phase 4 (approved)	TACR1
LANSOPRAZOLE	ChEMBL	Phase 4 (approved)	TACR1
MICONAZOLE	ChEMBL	Phase 4 (approved)	TACR1
NEFAZODONE	ChEMBL	Phase 4 (approved)	TACR1
NETUPITANT	ChEMBL	Phase 4 (approved)	TACR1
NILOTINIB	ChEMBL	Phase 4 (approved)	TACR1
PAROXETINE	ChEMBL	Phase 4 (approved)	TACR1
RITONAVIR	ChEMBL	Phase 4 (approved)	TACR1
TAMOXIFEN	ChEMBL	Phase 4 (approved)	TACR1
TERFENADINE	ChEMBL	Phase 4 (approved)	TACR1
THIOTHIXENE	ChEMBL	Phase 4 (approved)	TACR1
TRAZODONE	ChEMBL	Phase 4 (approved)	TACR1
CASOPITANT	ChEMBL	Phase 3	TACR1
SAREDUTANT	ChEMBL	Phase 3	TACR1
SERLOPITANT	ChEMBL	Phase 3	TACR1
BEFETUPITANT	ChEMBL	Phase 2	TACR1
DAPITANT	ChEMBL	Phase 2	TACR1
DNK333	ChEMBL	Phase 2	TACR1
LANEPITANT	ChEMBL	Phase 2	TACR1
ORVEPITANT	ChEMBL	Phase 2	TACR1
OSANETANT	ChEMBL	Phase 2	TACR1
SPERGUALIN	ChEMBL	Phase 2	TACR1
TALNETANT	ChEMBL	Phase 2	TACR1
TELMAPITANT	ChEMBL	Phase 2	TACR1
VESTIPITANT	ChEMBL	Phase 2	TACR1
VOFOPITANT	ChEMBL	Phase 2	TACR1
Alogliptin	PubChem	Approved	TACR1
Belzutifan	PubChem	Approved	TACR1
Propoxyphene	PubChem	Approved	TACR1
Tiotropium Bromide Monohydrate	PubChem	Approved	TACR1