Details of the Drug Combination

General Information of Drug Combination (ID: DCW90PT)

• Drug Combination Name: NARINGENIN + Azatadine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  NARINGENIN (DMHAZLM): Small molecular drug
  Azatadine (DMZ80SB): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 11.46
  Bliss Independence Score: 11.46
  Loewe Additivity Score: 27.77
  LHighest Single Agent (HSA) Score: 27.77

Molecular Interaction Atlas of This Drug Combination

NARINGENIN Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[4]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)	TTIWB6L	DHB1_HUMAN	Inhibitor	[5]
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Inhibitor	[6]
Lactoylglutathione lyase (GLO1)	TTV9A7R	LGUL_HUMAN	Inhibitor	[7]
Cytochrome P450 1B1 (CYP1B1)	TTI84H7	CP1B1_HUMAN	Inhibitor	[8]

NARINGENIN 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]

NARINGENIN Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 105D7 (cyp105)	DECV2ME	CYP28_STRAW	Metabolism	[10]

Indication(s) of Azatadine

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[2]
Common cold	CA00	Approved	[3]
Seasonal allergic rhinitis	CA08.01	Approved	[3]
Urticaria	EB00-EB05	Approved	[3]
Vasomotor/allergic rhinitis	CA08	Approved	[3]
Pruritus	EC90	Investigative	[3]

Azatadine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histamine H1 receptor (H1R)	TTTIBOJ	HRH1_HUMAN	Antagonist	[11]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] 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: 7119).
• [3] Azatadine FDA Label
• [4] Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
• [5] Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries. J Med Chem. 2008 Jul 24;51(14):4188-99.
• [6] Subtle side-chain modifications of the hop phytoestrogen 8-prenylnaringenin result in distinct agonist/antagonist activity profiles for estrogen re... J Med Chem. 2006 Dec 14;49(25):7357-65.
• [7] Structure-activity relationship of human GLO I inhibitory natural flavonoids and their growth inhibitory effects. Bioorg Med Chem. 2008 Apr 1;16(7):3969-75.
• [8] Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorg Med Chem. 2010 Sep 1;18(17):6310-5.
• [9] Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med. 2004 Mar 1;36(5):592-604.
• [10] The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.
• [11] Comparative effects of loratadine and azatadine in the treatment of seasonal allergic rhinitis. Asian Pac J Allergy Immunol. 1990 Dec;8(2):103-7.