Casopitant

Summary

Casopitant (CHEMBL1672054) is a phase-3 clinical-stage small molecule (ATC A04AD13) targeting TACR1; indicated across 10 conditions including insomnia and overactive bladder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: A04AD13
• Targets: 1 (TACR1)
• Indications: 10 conditions
• Clinical trials: 29
• Chemistry: 616.6 Da · C30H35F7N4O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1672054
Name	Casopitant
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	9917021
ATC	A04AD13
Molecular formula	C30H35F7N4O2
Molecular weight	616.6
InChIKey	XGGTZCKQRWXCHW-WMTVXVAQSA-N

SMILES: CC1=C(C=CC(=C1)F)[C@H]2C[C@H](CCN2C(=O)N(C)[C@H](C)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)N4CCN(CC4)C(=O)C

IUPAC name: (2R,4S)-4-(4-acetylpiperazin-1-yl)-N-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-(4-fluoro-2-methylphenyl)-N-methylpiperidine-1-carboxamide

Also known as: Casopitant, GW-679769, Gw679769, GW679769, Rezonic, Zunrisa, CASOPITANT

Parent form; salt/anhydrous children: CHEMBL2107320, CHEMBL3542382

Patent coverage: 530 distinct patent families (1,417 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,402 (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
TACR1	NK1 receptor	Antagonist	9.4	0.7%	P25103

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Substance-P receptor, Sigma non-opioid intracellular receptor 1, Cytochrome P450 3A4.

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
TACR1	9.9	Ki	0.13	nM	CHEMBL_ACT_5232430
TACR1	9.48	Ki	0.33	nM	CHEMBL_ACT_5232374
SIGMAR1	5.53	Ki	2980	nM	CHEMBL_ACT_5232400
CYP3A4	5.31	Ki	4930	nM	CHEMBL_ACT_15450900
CYP3A4	5.01	IC50	9860	nM	CHEMBL_ACT_15450854
CYP3A4	5.01	IC50	9720	nM	CHEMBL_ACT_15450855

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

10 indications (0 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
insomnia	2	MONDO:0013600	EFO:0004698
overactive bladder	2	MONDO:0006624	EFO:1000781
dyspepsia	2	MONDO:0002268	EFO:0008533
major depressive disorder	2	MONDO:0002009	MONDO:0002009
sleep disorder	2	MONDO:0100081	EFO:0008568

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

Clinical trials

Total trials: 29.

Phase distribution

Phase	Trials
PHASE2	12
PHASE1	11
PHASE3	5
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00326248	PHASE3	COMPLETED	Casopitant (Oral) And ZOFRAN To Prevent Postoperative Nausea And Vomiting In Women
NCT00334152	PHASE3	COMPLETED	Casopitant And ZOFRAN To Prevent Post Operative Nausea And Vomiting In Women
NCT00366834	PHASE3	COMPLETED	Intravenous And Oral Casopitant (GW679769) For The Prevention Of Chemotherapy Induced Nausea And Vomiting
NCT00431236	PHASE3	COMPLETED	A Study of the Drug Casopitant for the Prevention of Nausea Caused By Cisplatin-Based Highly Emetogenic Chemotherapy
NCT00601172	PHASE3	COMPLETED	A Study Of IV Casopitant For The Prevention Of Chemotherapy Induced Nausea And Vomiting.
NCT00102492	PHASE2	COMPLETED	Study Of GW679769 In Major Depressive Disorder
NCT00104403	PHASE2	COMPLETED	Study Of Prevention of Chemo-Induced Nausea and Vomiting Caused By Moderately Emetogenic Chemotherapy
NCT00169572	PHASE2	COMPLETED	Study for The Prevention Of Nausea in Cancer Patients Receiving Highly Emetogenic Cisplatin Based Chemotherapy
NCT00274690	PHASE2	COMPLETED	Post-Operative Nausea And Vomiting Study In Female Patients
NCT00280423	PHASE2	COMPLETED	Effects Of GW679769 On Sleep Onset And Maintenance And Next Day Functioning In Subjects With Primary Insomnia
NCT00280436	PHASE2	COMPLETED	Effects Of GW679769 On Sleep Onset And Maintenance,And Next Day Functioning In The Elderly And Non-elderly With Primary Insomnia
NCT00321477	PHASE2	COMPLETED	A Study Of GW679769 Compared To Placebo In Women With Overactive Bladder
NCT00332319	PHASE2	TERMINATED	Effects Of GW679769 On Bladder Nerve Function And Symptoms Of Overactive Bladder In Spinal Cord Injury Patients
NCT00354809	PHASE2	COMPLETED	Evaluation of A Morning Dosing Of A New Medicine And Its Effects On Sleep At Bedtime In Subjects With Primary Insomnia
NCT00358410	PHASE2	COMPLETED	An Exploratory Study Examining The Effects Of Taking GW679769 Once-Daily For 4 Days In Patients With Functional Dyspepsia
NCT00413023	PHASE2	COMPLETED	Study Of The Effects Of A New Antidepressant Therapy In Patients With Major Depressive Disorder (MDD)
NCT00650871	PHASE2	COMPLETED	A Study to Evaluate the Effects of GW679769 on Sleep and Cognitive Function in Subjects With Primary Insomnia
NCT00332046	PHASE1	COMPLETED	fMRI Study Comparing BOLD Activation Patterns Using GW679769 In Subjects With Social Anxiety Disorder
NCT00334646	PHASE1	TERMINATED	Cyclophosphamide Drug Interaction Study In Cancer Patients
NCT00358813	PHASE1	COMPLETED	Observational Pharmacokinetic Study Of GW679769 In Subjects With Renal Impairment
NCT00359177	PHASE1	COMPLETED	Observational Study Evaluating The Processing Or Breakdown Of GW679769 In Subjects With Hepatic Impairment
NCT00404274	PHASE1	COMPLETED	A Study Testing the Effect and Safety of Casopitant (GW679769) While Taking Warfarin in Healthy Human Volunteers
NCT00404378	PHASE1	COMPLETED	Study Of Healthy Subjects To Assess The Effect Of Ketoconazole And The Way The Body Will React To Casopitant [GW679769]
NCT00405080	PHASE1	COMPLETED	A Study in Healthy Subjects to Assess How Dosing of Rifampin Affects What the Body Does to a Dose of GW679769 (Casopitant).
NCT00437229	PHASE1	COMPLETED	A Study to Assess the Safety & Interaction Between GW679769, Dexamethasone, & Ondansetron When Taken by Healthy Adults
NCT00440128	PHASE1	COMPLETED	The Effects Of GW679769 (Casopitant) On The Pharmacokinetics Of Docetaxel In Subjects With Cancer
NCT00460707	PHASE1	COMPLETED	A Study to Assess the Safety and Interaction Between Casopitant and Ketoconazole When Taken By Healthy Adults
NCT00511823	PHASE1	COMPLETED	The Pharmacokinetic Interaction Between Oral Casopitant and Oral Dolasetron, Granisetron or Rosiglitazone in Subjects
NCT00264628	Not specified	COMPLETED	GW679769 In Fibromyalgia

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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
ROLAPITANT	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
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