netupitant Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
neurokinin NK1 (substance P) receptor antagonist	4898	290297-26-6

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: Ro 67-3189/000 netupitant	Netupitant is a selective antagonist of human substance P/neurokinin 1 (NK-1) receptors. Delayed emesis has been largely associated with the activation of tachykinin family neurokinin 1 (NK-1) receptors (broadly distributed in the central and peripheral nervous systems) by substance P. As shown in in vitro and in vivo studies, netupitant inhibits substance P mediated responses. Molecular weight: 578.60 Formula: C30H32F6N4O CLOGP: 6.51 LIPINSKI: 2 HAC: 5 HDO: 0 TPSA: 39.68 ALOGS: -5.31 ROTB: 7 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

Ro 67-3189/000
netupitant

Netupitant is a selective antagonist of human substance P/neurokinin 1 (NK-1) receptors. Delayed emesis has been largely associated with the activation of tachykinin family neurokinin 1 (NK-1) receptors (broadly distributed in the central and peripheral nervous systems) by substance P. As shown in in vitro and in vivo studies, netupitant inhibits substance P mediated responses.

Molecular weight: 578.60
Formula: C30H32F6N4O
CLOGP: 6.51
LIPINSKI: 2
HAC: 5
HDO: 0
TPSA: 39.68
ALOGS: -5.31
ROTB: 7

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
Vd (Volume of distribution)	5.54 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	2.83 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.00 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	34.28 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Oct. 10, 2014	FDA	HELSINN HLTHCARE

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

Pharmacologic Action:

Source	Code	Description
FDA MoA	N0000010262	Neurokinin 1 Antagonists
FDA EPC	N0000175786	Substance P/Neurokinin-1 Receptor Antagonist
FDA MoA	N0000182141	Cytochrome P450 3A4 Inhibitors
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000190113	Breast Cancer Resistance Protein Inhibitors
CHEBI has role	CHEBI:50919	antiemetico
CHEBI has role	CHEBI:55350	neurokinin-1 receptor antagonists

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Chemotherapy-induced nausea and vomiting	indication	236084000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	8.9	Basic
pKa2	3.35	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Substance-P receptor	GPCR	P25103	NK1R_HUMAN	ANTAGONIST	Ki	9.02		SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE

External reference:

ID	Source
D05152	KEGG_DRUG
4033795	VUID
N0000191094	NUI
4033795	VANDF
C1700730	UMLSCUI
CHEBI:85155	CHEBI
GAW	PDB_CHEM_ID
CHEMBL206253	ChEMBL_ID
DB09048	DRUGBANK_ID
C508854	MESH_SUPPLEMENTAL_RECORD_UI
5742	IUPHAR_LIGAND_ID
8409	INN_ID
7732P08TIR	UNII
6451149	PUBCHEM_CID
1552337	RXNORM
30612	MMSL
d08299	MMSL
015714	NDDF
716123009	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
AKYNZEO	HUMAN PRESCRIPTION DRUG LABEL	2	69639-101	CAPSULE	300 mg	ORAL	NDA	26 sections