Details of the Drug Combination

General Information of Drug Combination (ID: DCZ0K1O)

Drug Combination Name
Trifluridine Pralatrexate
Indication
Disease Entry Status REF
Clear cell renal cell carcinoma Investigative [1]
Component Drugs Trifluridine   DMG2YBD Pralatrexate   DMAO80I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: CAKI-1
Zero Interaction Potency (ZIP) Score: 1.72
Bliss Independence Score: 4
Loewe Additivity Score: 3.18
LHighest Single Agent (HSA) Score: 4.49

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Trifluridine
Disease Entry ICD 11 Status REF
Herpetic keratitis 1F00.10 Approved [2]
Virus infection 1A24-1D9Z Approved [3]
Colon cancer 2B90.Z Investigative [2]
Trifluridine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Candida Thymidylate synthase (Candi TMP1) TTU6BFZ TYSY_CANAL Inhibitor [6]
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Trifluridine Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [7]
Concentrative nucleoside transporter 1 (SLC28A1) DT0EQPW S28A1_HUMAN Substrate [8]
Equilibrative nucleoside transporter 1 (SLC29A1) DTXD1TQ S29A1_HUMAN Substrate [8]
Equilibrative nucleoside transporter 2 (SLC29A2) DTW78DQ S29A2_HUMAN Substrate [8]
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Trifluridine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Thymidine phosphorylase (TYMP) DE4HCYL TYPH_HUMAN Metabolism [9]
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Trifluridine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [10]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [11]
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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 [12]
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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 [13]
Proton-coupled folate transporter (SLC46A1) DTDJEMI PCFT_HUMAN Substrate [13]
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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 [14]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Astrocytoma DCY946Z SNB-19 Investigative [1]
Glioma DCLCJVI SF-295 Investigative [1]
Renal cell carcinoma DCNVBID SN12C Investigative [1]
Carcinoma DC1CX9H MCF7 Investigative [15]
Adenocarcinoma DC45BCD OVCAR3 Investigative [16]
Adenocarcinoma DCS7MZU NCIH23 Investigative [16]
Adenocarcinoma DCPEG4L HCT-15 Investigative [16]
High grade ovarian serous adenocarcinoma DCB01JO OVCAR-4 Investigative [16]
Minimally invasive lung adenocarcinoma DCMUZ35 NCI-H322M Investigative [16]
Ovarian serous cystadenocarcinoma DCHPKY9 SK-OV-3 Investigative [16]
Pleural epithelioid mesothelioma DCCRGN6 NCI-H226 Investigative [16]
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⏷ Show the Full List of 11 DrugCom(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Trifluridine 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: 8697).
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 Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703.
7 Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9.
8 Lonsurf, INN-trifluridine/tipiracil.
9 Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest. 2008 Oct;26(8):794-9.
10 Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
11 Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5-fluorouracil in colon cancer cells. Int J Cancer. 2010 May 15;126(10):2457-68. doi: 10.1002/ijc.24943.
12 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
13 Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.
14 Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23.
15 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
16 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976