Details of the Drug Combination

General Information of Drug Combination (ID: DCA6MCY)

Drug Combination Name

MK-1775 Pralatrexate

Indication

Disease Entry	Status	REF
Ewing sarcoma	Investigative	[1]

Component Drugs

MK-1775 DM3WDZ5

Pralatrexate DMAO80I

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: TC-71

Zero Interaction Potency (ZIP) Score: 6.332

Bliss Independence Score: 5.345

Loewe Additivity Score: 2.564

LHighest Single Agent (HSA) Score: 6.016

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of MK-1775

MK-1775 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Wee1-like protein kinase (WEE1)	TTJFOAL	WEE1_HUMAN	Inhibitor	[7]
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MK-1775 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Phosphorylation	[6]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Response To Substance	[6]
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Indication(s) of Pralatrexate

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[4]
Peripheral T-cell lymphoma	2A90.C	Approved	[4]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[5]

Pralatrexate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[8]
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Pralatrexate Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Folate transporter 1 (SLC19A1)	DTOSN46	S19A1_HUMAN	Substrate	[9]
Proton-coupled folate transporter (SLC46A1)	DTDJEMI	PCFT_HUMAN	Substrate	[9]
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Pralatrexate Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Folylpolyglutamate synthase (FPGS)	DECWT2V	FOLC_HUMAN	Metabolism	[10]
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Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Hodgkin lymphoma	DC1OE1P	U-HO1	Investigative	[1]
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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	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: 7702).
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 6840).
5	Pralatrexate FDA Label
6	Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin Cancer Res. 2014 Aug 15;20(16):4274-88. doi: 10.1158/1078-0432.CCR-13-2858.
7	A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
8	Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
9	Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.
10	Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23.