Details of the Drug

General Information of Drug (ID: DMEKAYI)

Drug Name
Netupitant
Synonyms R-1124; NK1 antagonist (emesis), Roche; Ro-67-3189
Indication
Disease Entry ICD 11 Status REF
Chemotherapy-induced nausea MD90 Phase 3 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 578.6
Logarithm of the Partition Coefficient (xlogp) 6.8
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 10
ADMET Property
Clearance
The sytemic clearance of drug is 20.3 +/- 9.2 L/h []
Half-life
The concentration or amount of drug in body reduced by one-half in 96 hours [2]
Metabolism
The drug is metabolized via the CYP3A4 and to a lesser extent by CYP2C9 and CYP2D6 []
Unbound Fraction
The unbound fraction of drug in plasma is 0.003% [2]
Vd
The volume of distribution (Vd) of drug is 1982 +/- 906 L []
Chemical Identifiers
Formula
C30H32F6N4O
IUPAC Name
2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide
Canonical SMILES
CC1=CC=CC=C1C2=CC(=NC=C2N(C)C(=O)C(C)(C)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)N4CCN(CC4)C
InChI
InChI=1S/C30H32F6N4O/c1-19-8-6-7-9-23(19)24-17-26(40-12-10-38(4)11-13-40)37-18-25(24)39(5)27(41)28(2,3)20-14-21(29(31,32)33)16-22(15-20)30(34,35)36/h6-9,14-18H,10-13H2,1-5H3
InChIKey
WAXQNWCZJDTGBU-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
6451149
ChEBI ID
CHEBI:85155
CAS Number
290297-26-6
DrugBank ID
DB09048
TTD ID
D0G3YC
INTEDE ID
DR1141
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Substance-P receptor (TACR1) TTZPO1L NK1R_HUMAN Antagonist [3]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [4]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [5]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Chemotherapy-induced nausea
ICD Disease Classification MD90
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Substance-P receptor (TACR1) DTT TACR1 7.40E-01 0.02 0.07
Substance-P receptor (TACR1) DTT TACR1 8.57E-01 -0.02 -0.18
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 2.59E-01 6.29E-02 3.14E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 4.84E-01 -8.38E-02 -8.46E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 8.99E-01 -6.93E-03 -1.36E-02
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 9.21E-01 7.31E-03 6.10E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 4.66E-01 4.25E-02 1.20E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 4.75E-01 5.15E-02 3.64E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Netupitant (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Arn-509 DMT81LZ Major Increased metabolism of Netupitant caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [6]
Troleandomycin DMUZNIG Minor Decreased metabolism of Netupitant caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [7]
Pexidartinib DMS2J0Z Major Decreased metabolism of Netupitant caused by Pexidartinib mediated inhibition of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [8]
Talazoparib DM1KS78 Moderate Decreased clearance of Netupitant due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [9]
HKI-272 DM6QOVN Major Decreased metabolism of Netupitant caused by HKI-272 mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [10]
LY2835219 DM93VBZ Moderate Decreased metabolism of Netupitant caused by LY2835219 mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [11]
Tucatinib DMBESUA Minor Decreased metabolism of Netupitant caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [7]
Palbociclib DMD7L94 Moderate Decreased metabolism of Netupitant caused by Palbociclib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [12]
MK-8228 DMOB58Q Moderate Decreased metabolism of Netupitant caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [13]
OPC-34712 DMHG57U Major Decreased metabolism of Netupitant caused by OPC-34712 mediated inhibition of CYP450 enzyme. Depression [6A70-6A7Z] [14]
Polatuzumab vedotin DMF6Y0L Moderate Decreased metabolism of Netupitant caused by Polatuzumab vedotin mediated inhibition of CYP450 enzyme. Diffuse large B-cell lymphoma [2A81] [15]
Cannabidiol DM0659E Minor Decreased metabolism of Netupitant caused by Cannabidiol mediated inhibition of CYP450 enzyme. Epileptic encephalopathy [8A62] [12]
Bay 80-6946 DMLOS5R Moderate Decreased metabolism of Netupitant caused by Bay 80-6946 mediated inhibition of CYP450 enzyme. Follicular lymphoma [2A80] [16]
Tazemetostat DMWP1BH Major Decreased metabolism of Netupitant caused by Tazemetostat mediated inhibition of CYP450 enzyme. Follicular lymphoma [2A80] [17]
Ripretinib DM958QB Moderate Decreased metabolism of Netupitant caused by Ripretinib mediated inhibition of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [6]
Avapritinib DMK2GZX Major Decreased metabolism of Netupitant caused by Avapritinib mediated inhibition of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [12]
Daclatasvir DMSFK9V Moderate Decreased metabolism of Netupitant caused by Daclatasvir mediated inhibition of CYP450 enzyme. Hepatitis virus infection [1E50-1E51] [6]
MK-1439 DM215WE Minor Decreased metabolism of Netupitant caused by MK-1439 mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [18]
Cobicistat DM6L4H2 Minor Decreased metabolism of Netupitant caused by Cobicistat mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [7]
Levamlodipine DM92S6N Moderate Decreased metabolism of Netupitant caused by Levamlodipine mediated inhibition of CYP450 enzyme. Hypertension [BA00-BA04] [19]
Tasimelteon DMLOQ1V Moderate Decreased metabolism of Netupitant caused by Tasimelteon mediated inhibition of CYP450 enzyme. Insomnia [7A00-7A0Z] [20]
Naloxegol DML0B41 Major Decreased metabolism of Netupitant caused by Naloxegol mediated inhibition of CYP450 enzyme. Large intestine motility disorder [DB32] [12]
Pemigatinib DM819JF Major Decreased metabolism of Netupitant caused by Pemigatinib mediated inhibition of CYP450 enzyme. Liver cancer [2C12] [21]
Brigatinib DM7W94S Major Decreased metabolism of Netupitant caused by Brigatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [6]
Lurbinectedin DMEFRTZ Major Decreased metabolism of Netupitant caused by Lurbinectedin mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [22]
PF-06463922 DMKM7EW Moderate Decreased metabolism of Netupitant caused by PF-06463922 mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [12]
Pralsetinib DMWU0I2 Moderate Decreased metabolism of Netupitant caused by Pralsetinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [23]
Capmatinib DMYCXKL Moderate Decreased metabolism of Netupitant caused by Capmatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [24]
Idelalisib DM602WT Minor Decreased metabolism of Netupitant caused by Idelalisib mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [7]
GDC-0199 DMH0QKA Major Decreased metabolism of Netupitant caused by GDC-0199 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [6]
IPI-145 DMWA24P Moderate Decreased metabolism of Netupitant caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [25]
Acalabrutinib DM7GCVW Major Decreased metabolism of Netupitant caused by Acalabrutinib mediated inhibition of CYP450 enzyme. Mature B-cell lymphoma [2A85] [26]
Arry-162 DM1P6FR Moderate Decreased clearance of Netupitant due to the transporter inhibition by Arry-162. Melanoma [2C30] [6]
Selumetinib DMC7W6R Major Decreased metabolism of Netupitant caused by Selumetinib mediated inhibition of CYP450 enzyme. Melanoma [2C30] [27]
LGX818 DMNQXV8 Major Decreased metabolism of Netupitant caused by LGX818 mediated inhibition of CYP450 enzyme. Melanoma [2C30] [28]
Ubrogepant DM749I3 Moderate Decreased metabolism of Netupitant caused by Ubrogepant mediated inhibition of CYP450 enzyme. Migraine [8A80] [29]
Rimegepant DMHOAUG Moderate Decreased metabolism of Netupitant caused by Rimegepant mediated inhibition of CYP450 enzyme. Migraine [8A80] [30]
Deflazacort DMV0RNS Major Decreased metabolism of Netupitant caused by Deflazacort mediated inhibition of CYP450 enzyme. Muscular dystrophy [8C70] [12]
Fedratinib DM4ZBK6 Minor Decreased metabolism of Netupitant caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [31]
Entrectinib DMMPTLH Major Decreased metabolism of Netupitant caused by Entrectinib mediated inhibition of CYP450 enzyme. Non-small cell lung cancer [2C25] [12]
S-297995 DM26IH8 Moderate Decreased metabolism of Netupitant caused by S-297995 mediated inhibition of CYP450 enzyme. Opioid use disorder [6C43] [12]
Olaparib DM8QB1D Major Decreased metabolism of Netupitant caused by Olaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [6]
Abametapir DM2RX0I Moderate Decreased metabolism of Netupitant caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [32]
Darolutamide DMV7YFT Minor Decreased metabolism of Netupitant caused by Darolutamide mediated inhibition of CYP450 enzyme. Prostate cancer [2C82] [33]
Upadacitinib DM32B5U Moderate Decreased metabolism of Netupitant caused by Upadacitinib mediated inhibition of CYP450 enzyme. Rheumatoid arthritis [FA20] [34]
LDE225 DMM9F25 Major Decreased metabolism of Netupitant caused by LDE225 mediated inhibition of CYP450 enzyme. Skin cancer [2C30-2C37] [35]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Netupitant caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [12]
Larotrectinib DM26CQR Moderate Decreased clearance of Netupitant due to the transporter inhibition by Larotrectinib. Solid tumour/cancer [2A00-2F9Z] [6]
Fostamatinib DM6AUHV Moderate Decreased metabolism of Netupitant caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [36]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Netupitant due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [37]
Elagolix DMB2C0E Moderate Decreased metabolism of Netupitant caused by Elagolix mediated inhibition of CYP450 enzyme. Uterine fibroid [2E86] [38]
Fluticasone DMGCSVF Moderate Decreased metabolism of Netupitant caused by Fluticasone mediated inhibition of CYP450 enzyme. Vasomotor/allergic rhinitis [CA08] [6]
⏷ Show the Full List of 52 DDI Information of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5742).
2 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3 Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44.
4 Complementary pharmacokinetic profiles of netupitant and palonosetron support the rationale for their oral fixed combination for the prevention of chemotherapy-induced nausea and vomiting. J Clin Pharmacol. 2019 Apr;59(4):472-487.
5 Effect of netupitant, a highly selective NK?receptor antagonist, on the pharmacokinetics of palonosetron and impact of the fixed dose combination of netupitant and palonosetron when coadministered with ketoconazole, rifampicin, and oral contraceptives. Support Care Cancer. 2013 Oct;21(10):2879-87.
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