Details of the Drug Combination

General Information of Drug Combination (ID: DCMIFY5)

• Drug Combination Name: Entecavir + Interferon Alfa-2b
• Indication: Hepatitis B, Chronic; Status: Phase 4 [1]
• Component Drugs:
  Entecavir (DM7VTQO): Small molecular drug
  Interferon Alfa-2b (DMWCQP4): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Entecavir

Disease Entry	ICD 11	Status	REF
Hepatitis B virus infection	1E51.0	Approved	[2]

Entecavir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Hepatitis B virus Reverse transcriptase (HBV RT)	TTS5K1M	DPOL_HBVA3	Modulator	[4]

Entecavir Interacts with 9 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[5]
Organic anion transporter 2 (SLC22A7)	DT0OC1Q	S22A7_HUMAN	Substrate	[6]
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[5]
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[7]
Organic cation/carnitine transporter 2 (SLC22A5)	DT3HUVD	S22A5_HUMAN	Substrate	[5]
Concentrative nucleoside transporter 2 (SLC28A2)	DT82KPY	S28A2_HUMAN	Substrate	[5]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3)	DT4YL5R	S28A3_HUMAN	Substrate	[5]
Equilibrative nucleoside transporter 1 (SLC29A1)	DTXD1TQ	S29A1_HUMAN	Substrate	[5]
Equilibrative nucleoside transporter 2 (SLC29A2)	DTW78DQ	S29A2_HUMAN	Substrate	[5]

Indication(s) of Interferon Alfa-2b

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[3]

Interferon Alfa-2b Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Interferon-alpha 2 (IFNA2)	TTSIUJ9	IFNA2_HUMAN	Modulator	[9]

Interferon Alfa-2b Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
2'-5'-oligoadenylate synthase 1 (OAS1)	OT8ZLOCY	OAS1_HUMAN	Increases Expression	[8]
Interferon-induced, double-stranded RNA-activated protein kinase (EIF2AK2)	OT8DXMS3	E2AK2_HUMAN	Increases Expression	[8]
Tyrosine-protein kinase JAK1 (JAK1)	OT0X3D17	JAK1_HUMAN	Increases Expression	[8]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Increases Phosphorylation	[8]
Signal transducer and activator of transcription 1-alpha/beta (STAT1)	OTLMBUZ6	STAT1_HUMAN	Increases Expression	[8]
Signal transducer and activator of transcription 2 (STAT2)	OTO9G2RZ	STAT2_HUMAN	Increases Phosphorylation	[8]

References

• [1] ClinicalTrials.gov (NCT02360592) Combination Therapy With Interferon Plus Interleukin 2 and Hepatitis B Vaccine in Chronic Hepatitis B Patients
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Effect of hepatitis B virus reverse transcriptase variations on entecavir treatment response. J Infect Dis. 2014 Sep 1;210(5):701-7.
• [5] Multiple SLC and ABC Transporters Contribute to the Placental Transfer of Entecavir. Drug Metab Dispos. 2017 Mar;45(3):269-278.
• [6] Human organic anion transporter 2 is an entecavir, but not tenofovir, transporter. Drug Metab Pharmacokinet. 2017 Feb;32(1):116-119.
• [7] The oligopeptide transporter 2-mediated reabsorption of entecavir in rat kidney. Eur J Pharm Sci. 2014 Feb 14;52:41-7.
• [8] 6-Hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside potentiates the anti-proliferative effect of interferon / by promoting activation of the JAK/STAT signaling by inhibiting SOCS3 in hepatocellular carcinoma cells. Toxicol Appl Pharmacol. 2017 Dec 1;336:31-39. doi: 10.1016/j.taap.2017.10.004. Epub 2017 Oct 12.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.