Details of the Drug Combination

General Information of Drug Combination (ID: DCQYWDC)

• Drug Combination Name: NARINGENIN + Etonogestrel
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  NARINGENIN (DMHAZLM): Small molecular drug
  Etonogestrel (DMKA8J4): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 22.09
  Bliss Independence Score: 22.09
  Loewe Additivity Score: 38.22
  LHighest Single Agent (HSA) Score: 38.22

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	[3]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)	TTIWB6L	DHB1_HUMAN	Inhibitor	[4]
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Inhibitor	[5]
Lactoylglutathione lyase (GLO1)	TTV9A7R	LGUL_HUMAN	Inhibitor	[6]
Cytochrome P450 1B1 (CYP1B1)	TTI84H7	CP1B1_HUMAN	Inhibitor	[7]

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	[8]

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	[9]

Indication(s) of Etonogestrel

Disease Entry	ICD 11	Status	REF
Contraception	QA21	Approved	[2]

Etonogestrel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Progesterone receptor (PGR)	TTUV8G9	PRGR_HUMAN	Binder	[10]

Etonogestrel Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[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: 7590).
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorg Med Chem. 2010 Sep 1;18(17):6310-5.
• [8] Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med. 2004 Mar 1;36(5):592-604.
• [9] The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.
• [10] Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7.
• [11] The role of CYP2C and CYP3A in the disposition of 3-keto-desogestrel after administration of desogestrel. Br J Clin Pharmacol. 2005 Jul;60(1):69-75.