Details of the Drug Combination

General Information of Drug Combination (ID: DCF1ZR5)

• Drug Combination Name: Ribavirin-TP + Sitagliptin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Ribavirin-TP (DM09NGV): Small molecular drug
  Sitagliptin (DMGDKXN): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 50.09
  Bliss Independence Score: 50.09
  Loewe Additivity Score: 61.95
  LHighest Single Agent (HSA) Score: 61.95

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ribavirin-TP

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

Ribavirin-TP Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Hepatitis C virus NS3 helicase (HCV NS3)	TTWXB3E	POLG_HCV1	Inhibitor	[2]

Indication(s) of Sitagliptin

Disease Entry	ICD 11	Status	REF
Cystic fibrosis	CA25	Approved	[3]
Non-insulin dependent diabetes	5A11	Approved	[3]
Renal hypoplasia	N.A.	Approved	[3]
Type-2 diabetes	5A11	Approved	[4]
Peripheral arterial disease	BD4Z	Phase 1/2	[5]

Sitagliptin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dipeptidyl peptidase 4 (DPP-4)	TTDIGC1	DPP4_HUMAN	Inhibitor	[6]

Sitagliptin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[8]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[9]

Sitagliptin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[10]

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] ATP-binding domain of NTPase/helicase as a target for hepatitis C antiviral therapy. Acta Biochim Pol. 2000;47(1):173-80.
• [3] Sitagliptin FDA Label
• [4] 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: 6286).
• [5] ClinicalTrials.gov (NCT01619332) Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763. U.S. National Institutes of Health.
• [6] Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009 Oct;124(1):113-38.
• [7] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [8] 265 effect of dietary cholesterol on gallbladder bile lithogenicity and gene expression in the enterohepatic axis of non-obese gallstone and control women. Journal of Hepatology, 2009, 50(09):S105-S106.
• [9] Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein. J Pharmacol Exp Ther. 2007 May;321(2):673-83.
• [10] Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58.