Details of the Drug Combination

General Information of Drug Combination (ID: DCPM904)

Drug Combination Name

Sitagliptin PMID28870136-Compound-43

Indication

Disease Entry	Status	REF
Chronic myelogenous leukemia	Investigative	[1]

Component Drugs

Sitagliptin DMGDKXN

PMID28870136-Compound-43 DMWGV8N

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: KBM-7

Zero Interaction Potency (ZIP) Score: 1.83

Bliss Independence Score: 1.83

Loewe Additivity Score: 17.32

LHighest Single Agent (HSA) Score: 17.32

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Sitagliptin

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

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	[5]
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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	[6]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[7]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[8]
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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	[9]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[9]
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PMID28870136-Compound-43 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Ecto-5'-nucleotidase (CD73)	TTK0O6Y	5NTD_HUMAN	Inhibitor	[10]
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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	Sitagliptin FDA Label
3	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).
4	ClinicalTrials.gov (NCT01619332) Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763. U.S. National Institutes of Health.
5	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.
6	Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
7	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.
8	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.
9	Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58.
10	Ectonucleotidase inhibitors: a patent review (2011-2016).Expert Opin Ther Pat. 2017 Dec;27(12):1291-1304.