Details of the Drug Combination

General Information of Drug Combination (ID: DC9H6TV)

• Drug Combination Name: Aprepitant + Desloratadine
• Indication: Pruritus; Status: Phase 1 [1]
• Component Drugs:
  Aprepitant (DM053KT): Small molecular drug
  Desloratadine (DM56YN7): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

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]

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]

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]

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]

Indication(s) of Desloratadine

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[6]
Common cold	CA00	Approved	[7]
Seasonal allergic rhinitis	CA08.01	Approved	[7]
Vasomotor/allergic rhinitis	CA08	Approved	[7]
Allergic urticaria	N.A.	Investigative	[7]

Desloratadine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histamine H1 receptor (H1R)	TTTIBOJ	HRH1_HUMAN	Antagonist	[13]

Desloratadine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[14]

Desloratadine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[15]
UDP-glucuronosyltransferase 2B10 (UGT2B10)	DEI8NGH	UDB10_HUMAN	Metabolism	[15]

Desloratadine Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Histamine H1 receptor (HRH1)	OT8F9FV6	HRH1_HUMAN	Affects Binding	[16]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Increases Phosphorylation	[17]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[17]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[17]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[18]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[17]
Hippocalcin-like protein 1 (HPCAL1)	OTOBBFRD	HPCL1_HUMAN	Decreases Expression	[17]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[17]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Phosphorylation	[17]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[19]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Affects Binding	[20]
Glycylpeptide N-tetradecanoyltransferase 1 (NMT1)	OT42GQ3D	NMT1_HUMAN	Affects Response To Substance	[17]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Affects Chemical Synthesis	[21]

References

• [1] ClinicalTrials.gov (NCT04399148) Influence of Antipruritics on the Dermal Blood Flow Response to Histamine, Cinnamaldehyde and Capsaicin.
• [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: 7157).
• [7] Desloratadine 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] Examining the tolerability of the non-sedating antihistamine desloratadine: a prescription-event monitoring study in England. Drug Saf. 2009;32(2):169-79.
• [14] P-glycoprotein limits the brain penetration of nonsedating but not sedating H1-antagonists. Drug Metab Dispos. 2003 Mar;31(3):312-8.
• [15] Further characterization of the metabolism of desloratadine and its cytochrome P450 and UDP-glucuronosyltransferase inhibition potential: identification of desloratadine as a relatively selective UGT2B10 inhibitor. Drug Metab Dispos. 2015 Sep;43(9):1294-302.
• [16] Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
• [17] Blockade of NMT1 enzymatic activity inhibits N-myristoylation of VILIP3 protein and suppresses liver cancer progression. Signal Transduct Target Ther. 2023 Jan 9;8(1):14. doi: 10.1038/s41392-022-01248-9.
• [18] Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
• [19] 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.
• [20] Testing of the inhibitory effects of loratadine and desloratadine on SARS-CoV-2 spike pseudotyped virus viropexis. Chem Biol Interact. 2021 Apr 1;338:109420. doi: 10.1016/j.cbi.2021.109420. Epub 2021 Feb 18.
• [21] Effect of cyp2d6*10 allele on the pharmacokinetics of loratadine in chinese subjects. Drug Metab Dispos. 2005 Sep;33(9):1283-7. doi: 10.1124/dmd.105.005025. Epub 2005 Jun 2.