Details of the Drug Combination

General Information of Drug Combination (ID: DCBS5VQ)

• Drug Combination Name: Diphenhydramine + Lactose
• Indication: Breast Cancer; Status: Phase 3 [1]
• Component Drugs:
  Diphenhydramine (DMKQTBA): Small molecular drug
  Lactose (DMO4GPK): N.A.

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Diphenhydramine

Disease Entry	ICD 11	Status	REF
Hyperemesis gravidarum	N.A.	Approved	[2]
Insomnia	7A00-7A0Z	Approved	[2]
Meniere disease	AB31.0	Approved	[3]
Nausea	MD90	Approved	[2]
Seasonal allergic rhinitis	CA08.01	Approved	[2]
Vasomotor/allergic rhinitis	CA08	Approved	[2]
Vomiting	MD90	Approved	[2]

Diphenhydramine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histamine N-methyltransferase (HNMT)	TT2B6EV	HNMT_HUMAN	Inhibitor	[5]
Histamine H1 receptor (H1R)	TTTIBOJ	HRH1_HUMAN	Antagonist	[6]

Diphenhydramine Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[9]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[9]

Diphenhydramine Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Decreases Activity	[10]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Decreases Expression	[11]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[11]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[11]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[11]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Decreases Expression	[11]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[11]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Activity	[12]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Decreases Expression	[11]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[11]

Indication(s) of Lactose

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[4]

Lactose Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Influenza Neuraminidase (Influ NA)	TT50QJ3	NRAM_I33A0	Inhibitor	[4]

Lactose Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cellobiose 2-epimerase (CE)	DEGLW18	A0A173SS24_9FIRM	Metabolism	[13]
Cellobiose 2-epimerase (CE)	DENTGJO	A0A173Z970_9FIRM	Metabolism	[13]
Cellobiose 2-epimerase (CE)	DE4XLDR	A0A174ZCD1_9FIRM	Metabolism	[13]
Cellobiose 2-epimerase (CE)	DEGBVKJ	A9KK53_LACP7	Metabolism	[13]
Cellobiose 2-epimerase (CE)	DEDY9F6	CEEP_EUBCE	Metabolism	[13]
Beta-galactosidase (bgaB)	DEQB4LT	A0A2U1B4D0_9BACT	Metabolism	[14]

References

• [1] ClinicalTrials.gov (NCT04237090) Feasibility of a Clinical Trial Comparing the Use of Cetirizine to Replace Diphenhydramine in the Prevention of Reactions Related to Paclitaxel
• [2] Diphenhydramine FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [6] Intact cell binding for in vitro prediction of sedative and non-sedative histamine H1-receptor antagonists based on receptor internalization. J Pharmacol Sci. 2008 May;107(1):66-79.
• [7] Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metab Dispos. 2007 Jan;35(1):72-8.
• [8] Pharmacogenomics in psychiatry: implications for practice. Recent Pat Biotechnol. 2014;8(2):152-9.
• [9] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [10] Cholinesterase inhibition by phenothiazine and nonphenothiazine antihistaminics: analysis of its postulated role in synergizing organophosphate toxicity. Toxicol Appl Pharmacol. 1975 Feb;31(2):179-90.
• [11] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [12] First-generation antihistamines diphenhydramine and chlorpheniramine reverse cytokine-afforded eosinophil survival by enhancing apoptosis. Allergy Asthma Proc. 2007 Jan-Feb;28(1):79-86. doi: 10.2500/aap.2007.28.2961.
• [13] Cloning and sequencing of the gene for cellobiose 2-epimerase from a ruminal strain of Eubacterium cellulosolvens. FEMS Microbiol Lett. 2008 Oct;287(1):34-40.
• [14] Identification and characterization of a novel beta-galactosidase from Victivallis vadensis ATCC BAA-548, an anaerobic fecal bacterium. J Microbiol. 2012 Dec;50(6):1034-40.