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Details

Stereochemistry ABSOLUTE
Molecular Formula C30H35F7N4O2
Molecular Weight 616.6133
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CASOPITANT

SMILES

C[C@@H](N(C)C(=O)N1CC[C@@H](C[C@@H]1C2=CC=C(F)C=C2C)N3CCN(CC3)C(C)=O)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F

InChI

InChIKey=XGGTZCKQRWXCHW-WMTVXVAQSA-N
InChI=1S/C30H35F7N4O2/c1-18-13-24(31)5-6-26(18)27-17-25(40-11-9-39(10-12-40)20(3)42)7-8-41(27)28(43)38(4)19(2)21-14-22(29(32,33)34)16-23(15-21)30(35,36)37/h5-6,13-16,19,25,27H,7-12,17H2,1-4H3/t19-,25+,27-/m1/s1

HIDE SMILES / InChI
Molecular Formula C30H35F7N4O2
Molecular Weight 616.6133
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19445564 | http://adisinsight.springer.com/drugs/800018590

Casopitant (GW679769) is a novel substituted piperidine derivative that competitively binds with NK1 receptors. The full occupancy of the receptor by their piperidine compound inhibits its binding with tachykinin neurotransmitters, including SP. Casopitant, in a series of in vitro and in vivo experimentations, has exhibited a potent NK1 receptor antagonism. On 29 May 2008, GlaxoSmithKline announced the submission of a new drug application to the FDA for intravenous and oral formulations of casopitant mesylate. This drug was proposed for the prevention of chemotherapy-induced nausea and vomiting as an add-on therapy to the standard dual therapy of 5-HT3 receptor antagonists + dexamethasone. The submission also included a proposed indication for postoperative nausea and vomiting prevention. Rezonic™ is the proposed trade name for casopitant mesylate in the United States; Zunrisa™ is the proposed trade name for casopitant mesylate for GlaxoSmithKline’s global group of companies. In September 2009, GlaxoSmithKline decided to discontinue all regulatory filings for casopitant based on an estimate of the amount of additional safety data.

CNS Activity

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2849
 10.2 null [pKi]
Inhibitor
8504
 9.86 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Phase III
665
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2080 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19420128/
90 mg single, intravenous
dose: 90 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CASOPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
761 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19420128/
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CASOPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6980 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19420128/
90 mg single, intravenous
dose: 90 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CASOPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
6620 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19420128/
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CASOPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15.6 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19420128/
90 mg single, intravenous
dose: 90 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CASOPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
17 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19420128/
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CASOPITANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.4%
OTHER GOV'T
https://www.ema.europa.eu/en/documents/withdrawal-report/withdrawal-assessment-report-zunrisa_en.pdf
unknown, unknown
 CASOPITANT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
Why receptor reserve matters for neurokinin1 (NK1) receptor antagonists.
2013-12
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clinical candidate.
2011-02-24
A novel and integrated approach for the identification and characterization of drug-induced cardiac toxicity in the dog.
2011-02
Management of chemotherapy-induced nausea and vomiting.
2010-12-07
The evaluation of drug rechallenge: the casopitant Phase III program.
2010-12
Determination of casopitant and its three major metabolites in dog and rat plasma by positive ion liquid chromatography/tandem mass spectrometry.
2010-11-01
Casopitant improves the quality of life in patients receiving highly emetogenic chemotherapy.
2010-11
Effect of single and repeat doses of casopitant on the pharmacokinetics of CYP450 3A4 substrates midazolam and nifedipine.
2010-10
Metabolic disposition of casopitant, a potent neurokinin-1 receptor antagonist, in mice, rats, and dogs.
2010-10
Quantitation of a de-fluorinated analogue of casopitant mesylate by normal-phase liquid chromatography/mass spectrometry.
2010-09-15
Neurokinin-1 receptor antagonists: a comprehensive patent survey.
2010-08
Ketoconazole and rifampin significantly affect the pharmacokinetics, but not the safety or QTc interval, of casopitant, a neurokinin-1 receptor antagonist.
2010-08
Phase II study to evaluate the safety and efficacy of the oral neurokinin-1 receptor antagonist casopitant (GW679769) administered with ondansetron for the prevention of postoperative and postdischarge nausea and vomiting in high-risk patients.
2010-07
Winning a won game: caffeine panacea for obesity syndemic.
2010-06
Effect of casopitant, a novel NK-1 receptor antagonist, on the pharmacokinetics and pharmacodynamics of steady-state warfarin.
2010-05
Phase 2 trial results with the novel neurokinin-1 receptor antagonist casopitant in combination with ondansetron and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting in cancer patients receiving moderately emetogenic chemotherapy.
2009-12-15
Tachykinin receptor antagonists in clinical trials.
2009-12
Phase III trial of casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy.
2009-11-10
Randomized, double-blind, dose-ranging trial of the oral neurokinin-1 receptor antagonist casopitant mesylate for the prevention of cisplatin-induced nausea and vomiting.
2009-11
Impact of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of ondansetron and dexamethasone.
2009-09
Effect of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of dolasetron and granisetron.
2009-09
Disposition and metabolism of radiolabeled casopitant in humans.
2009-08
Casopitant: a new warrior in the antiemetic crusade.
2009-06
Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial.
2009-06
Casopitant: a novel NK(1)-receptor antagonist in the prevention of chemotherapy-induced nausea and vomiting.
2009-04
Antiemetic control: toward a new standard of care for emetogenic chemotherapy.
2009-03
Management of postoperative nausea and vomiting: focus on palonosetron.
2009-02
Pharmacological management of chemotherapy-induced nausea and vomiting: focus on recent developments.
2009
(S)-1-[3,5-Bis-(trifluoro-meth-yl)phen-yl]-N-methylethyl-amine-(R)-2-hydroxy-butane-dioic acid (1/1).
2008-12-24
Pharmacokinetics and brain penetration of casopitant, a potent and selective neurokinin-1 receptor antagonist, in the ferret.
2008-09
Casopitant, a neurokinin-1 receptor antagonist with anti-emetic and anti-nausea activities.
2008-07
Chemotherapy-induced nausea and vomiting.
2008-04-09
Novel neurokinin-1 antagonists as antiemetics for the treatment of chemotherapy-induced emesis.
2006-04-01
Patents

Patents

07060702
2

Sample Use Guides

In Vivo Use Guide
A single 100 or 150 mg dose schedule of casopitant, orally or intravenously
Route of Administration: Other
In Vitro Use Guide
Casopitant inhibited CYP3A4 activity in human liver microsomes with an IC50 lower than 10 uM.
Substance Class Chemical
Created
by admin
on Wed Apr 02 07:48:23 GMT 2025
Edited
by admin
on Wed Apr 02 07:48:23 GMT 2025
Record UNII
3B03KPM27L
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CASOPITANT
INN   MART.   WHO-DD  
INN  
Official Name English
GW-679769
Preferred Name English
CASOPITANT [MART.]
Common Name English
casopitant [INN]
Common Name English
GW679769
Code English
Casopitant [WHO-DD]
Common Name English
Classification Tree Code System Code
WHO-VATC QA04AD13
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
NCI_THESAURUS C265
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
WHO-ATC A04AD13
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
Code System Code Type Description
NCI_THESAURUS
C71635
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
EVMPD
SUB32122
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
MESH
C531951
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
EPA CompTox
DTXSID40961762
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
DRUG CENTRAL
4401
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
FDA UNII
3B03KPM27L
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
ChEMBL
CHEMBL1672054
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
PUBCHEM
9917021
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
CAS
414910-27-3
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
SMS_ID
100000124413
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
DRUG BANK
DB06634
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
WIKIPEDIA
CASOPITANT
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
INN
8701
Created by admin on Wed Apr 02 07:48:23 GMT 2025 , Edited by admin on Wed Apr 02 07:48:23 GMT 2025
PRIMARY
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
MAJOR
Structure of CASOPITANT MESYLATE
SALT/SOLVATE -> PARENT
SUBSTANCE-P RECEPTOR
TARGET -> INHIBITOR
Related Record Type Details
Structure of (2R,4S)-4-((2-(ACETYLAMINO)ETHYL)AMINO)-N-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHYL)-2-(4-FLUORO-2-METHYLPHENYL)-N-METHYL-1-PIPERIDINECARBOXAMIDE
METABOLITE -> PARENT
FECAL; PLASMA
Structure of 1-PIPERIDINECARBOXAMIDE, 4-(4-ACETYL-1-PIPERAZINYL)-N-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHYL)-2-(4-FLUORO-2-(HYDROXYMETHYL)PHENYL)-N-METHYL-, (2R,4S)-
METABOLITE -> PARENT
after oral administration, at 1h
PLASMA
Structure of (2R,4S)-4-AMINO-N-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHYL)-2-(4-FLUORO-2-METHYLPHENYL)-N-METHYL-1-PIPERIDINECARBOXAMIDE
METABOLITE -> PARENT
FECAL; PLASMA
Structure of .BETA.-D-GLUCOPYRANOSIDURONIC ACID, (1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHYL
METABOLITE -> PARENT
PLASMA
Structure of (2R,4S)-4-(4-ACETYL-3-HYDROXY-1-PIPERAZINYL)-N-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHYL)-2-(4-FLUORO-2-METHYLPHENYL)-N-METHYL-1-PIPERIDINECARBOXAMIDE
METABOLITE -> PARENT
after oral administration, at 1h
MAJOR
PLASMA
Structure of (2R,4S)-N-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHYL)-2-(4-FLUORO-2-METHYLPHENYL)-N-METHYL-4-(3-OXO-1-PIPERAZINYL)-1-PIPERIDINECARBOXAMIDE
METABOLITE -> PARENT
after oral administration, at 1h
MAJOR
PLASMA
Structure of .BETA.-D-GLUCOPYRANOSIDURONIC ACID, (1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHYL
METABOLITE -> PARENT
MAJOR
URINE
Related Record Type Details
Structure of CASOPITANT
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION

Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

Tmax PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

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