Details of the Drug Combination

General Information of Drug Combination (ID: DCP2LMK)

Drug Combination Name
Aprepitant Palonosetron
Indication
Disease Entry Status REF
Postoperative Nausea and Vomiting Phase 1 [1]
Component Drugs Aprepitant   DM053KT Palonosetron   DMBHMOX
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Aprepitant
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [2]
Nausea MD90 Approved [3]
Vomiting MD90 Approved [4]
Solid tumour/cancer 2A00-2F9Z Phase 3 [5]
Aprepitant Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Substance-P receptor (TACR1) TTZPO1L NK1R_HUMAN Antagonist [8]
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Aprepitant Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
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Aprepitant Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [11]
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Aprepitant Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Decreases Phosphorylation [12]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [12]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [12]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [12]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Expression [12]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [12]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Palonosetron
Disease Entry ICD 11 Status REF
Nausea MD90 Approved [6]
Vomiting MD90 Approved [7]
Palonosetron Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
5-HT 3A receptor (HTR3A) TTPC4TU 5HT3A_HUMAN Antagonist [13]
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Palonosetron Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [14]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [15]
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Palonosetron Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [16]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Leukemia DCMQ9DD N. A. Phase 1 [17]
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References

1 ClinicalTrials.gov (NCT02597907) Postoperative Nausea and Vomiting: Ramosetron Plus Aprepitant vs Palonosetron Plus Aprepitant
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 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: 3490).
4 Aprepitant FDA Label
5 ClinicalTrials.gov (NCT00571168) Efficacy and Safety of Aprepitant in Subjects With Multiple Myeloma During and After High-dose Chemotherapy. U.S. National Institutes of Health.
6 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: 7486).
7 Palonosetron FDA Label
8 Potent, brain-penetrant, hydroisoindoline-based human neurokinin-1 receptor antagonists. J Med Chem. 2009 May 14;52(9):3039-46.
9 Improving the prediction of the brain disposition for orally administered drugs using BDDCS. Adv Drug Deliv Rev. 2012 Jan;64(1):95-109.
10 Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients. Cancer Chemother Pharmacol. 2005 Jun;55(6):609-16.
11 Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos. 2004 Nov;32(11):1287-92.
12 Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-B axis: Shedding new light on resistance to Aprepitant. Int J Biochem Cell Biol. 2018 Oct;103:105-114. doi: 10.1016/j.biocel.2018.08.010. Epub 2018 Aug 23.
13 Management of postoperative nausea and vomiting: focus on palonosetron. Ther Clin Risk Manag. 2009 Feb;5(1):21-34.
14 Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Biopharm Drug Dispos. 2004 Nov;25(8):329-37.
15 Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Med Sci Monit. 2005 Oct;11(10):RA322-8.
16 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
17 ClinicalTrials.gov (NCT00415103) AMENO-2: Aprepitant Plus Palonosetron Versus Granisetron in the Prevention of Nausea and the Emesis Induced by Chemotherapy in Patients Treated With Haematopoietic Progenitors