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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=C(C)C=C(F)C=C2)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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
10.2 null [pKi]
9.86 µM [IC50]
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
Novel neurokinin-1 antagonists as antiemetics for the treatment of chemotherapy-induced emesis.
2006 Apr 1
(S)-1-[3,5-Bis-(trifluoro-meth-yl)phen-yl]-N-methylethyl-amine-(R)-2-hydroxy-butane-dioic acid (1/1).
2008 Dec 24
Casopitant, a neurokinin-1 receptor antagonist with anti-emetic and anti-nausea activities.
2008 Jul
Chemotherapy-induced nausea and vomiting.
2008 Mar-Apr
Pharmacokinetics and brain penetration of casopitant, a potent and selective neurokinin-1 receptor antagonist, in the ferret.
2008 Sep
Pharmacological management of chemotherapy-induced nausea and vomiting: focus on recent developments.
2009
Casopitant: a novel NK(1)-receptor antagonist in the prevention of chemotherapy-induced nausea and vomiting.
2009 Apr
Disposition and metabolism of radiolabeled casopitant in humans.
2009 Aug
Tachykinin receptor antagonists in clinical trials.
2009 Dec
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 Dec 15
Management of postoperative nausea and vomiting: focus on palonosetron.
2009 Feb
Casopitant: a new warrior in the antiemetic crusade.
2009 Jun
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 Jun
Antiemetic control: toward a new standard of care for emetogenic chemotherapy.
2009 Mar
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 Nov 10
Impact of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of ondansetron and dexamethasone.
2009 Sep
Effect of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of dolasetron and granisetron.
2009 Sep
Ketoconazole and rifampin significantly affect the pharmacokinetics, but not the safety or QTc interval, of casopitant, a neurokinin-1 receptor antagonist.
2010 Aug
The evaluation of drug rechallenge: the casopitant Phase III program.
2010 Dec
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 Jul
Winning a won game: caffeine panacea for obesity syndemic.
2010 Jun
Effect of casopitant, a novel NK-1 receptor antagonist, on the pharmacokinetics and pharmacodynamics of steady-state warfarin.
2010 May
Casopitant improves the quality of life in patients receiving highly emetogenic chemotherapy.
2010 Nov
Effect of single and repeat doses of casopitant on the pharmacokinetics of CYP450 3A4 substrates midazolam and nifedipine.
2010 Oct
Metabolic disposition of casopitant, a potent neurokinin-1 receptor antagonist, in mice, rats, and dogs.
2010 Oct
Management of chemotherapy-induced nausea and vomiting.
2010 Sep-Oct
A novel and integrated approach for the identification and characterization of drug-induced cardiac toxicity in the dog.
2011 Feb
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 Feb 24
Why receptor reserve matters for neurokinin1 (NK1) receptor antagonists.
2013 Dec
Patents

Patents

Sample Use Guides

A single 100 or 150 mg dose schedule of casopitant, orally or intravenously
Route of Administration: Other
Casopitant inhibited CYP3A4 activity in human liver microsomes with an IC50 lower than 10 uM.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:25:25 GMT 2023
Edited
by admin
on Sat Dec 16 16:25:25 GMT 2023
Record UNII
3B03KPM27L
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CASOPITANT
INN   MART.   WHO-DD  
INN  
Official Name English
CASOPITANT [MART.]
Common Name English
casopitant [INN]
Common Name English
GW679769
Code English
Casopitant [WHO-DD]
Common Name English
GW-679769
Code English
Classification Tree Code System Code
WHO-VATC QA04AD13
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
NCI_THESAURUS C265
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
WHO-ATC A04AD13
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C71635
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
EVMPD
SUB32122
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
MESH
C531951
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
EPA CompTox
DTXSID40961762
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
DRUG CENTRAL
4401
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
FDA UNII
3B03KPM27L
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
ChEMBL
CHEMBL1672054
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
PUBCHEM
9917021
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
CAS
414910-27-3
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
SMS_ID
100000124413
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
DRUG BANK
DB06634
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
WIKIPEDIA
CASOPITANT
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
INN
8701
Created by admin on Sat Dec 16 16:25:27 GMT 2023 , Edited by admin on Sat Dec 16 16:25:27 GMT 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
Related Record Type Details
METABOLITE -> PARENT
FECAL; PLASMA
METABOLITE -> PARENT
after oral administration, at 1h
PLASMA
METABOLITE -> PARENT
FECAL; PLASMA
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
after oral administration, at 1h
MAJOR
PLASMA
METABOLITE -> PARENT
after oral administration, at 1h
MAJOR
PLASMA
METABOLITE -> PARENT
MAJOR
URINE
Related Record Type Details
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