Details of the Drug Combination

General Information of Drug Combination (ID: DC78RPH)

Drug Combination Name
Indazole derivative 5 Trifluridine
Indication
Disease Entry Status REF
Renal cell carcinoma Investigative [1]
Component Drugs Indazole derivative 5   DMM1I8R Trifluridine   DMG2YBD
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SN12C
Zero Interaction Potency (ZIP) Score: 5.31
Bliss Independence Score: 4.56
Loewe Additivity Score: 3.34
LHighest Single Agent (HSA) Score: 6.31

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indazole derivative 5 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
ABL T315I mutant (ABL T315I) TTZJTWA ABL1_HUMAN Inhibitor [4]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I) TTIV39N BCR_HUMAN-ABL1_HUMAN Inhibitor [4]
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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 [5]
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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 [6]
Concentrative nucleoside transporter 1 (SLC28A1) DT0EQPW S28A1_HUMAN Substrate [7]
Equilibrative nucleoside transporter 1 (SLC29A1) DTXD1TQ S29A1_HUMAN Substrate [7]
Equilibrative nucleoside transporter 2 (SLC29A2) DTW78DQ S29A2_HUMAN Substrate [7]
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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 [8]
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Trifluridine Interacts with 7 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 [9]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [10]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Increases Cleavage [11]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [11]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [11]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Cleavage [11]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Activity [12]
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⏷ Show the Full List of 7 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DCIKOE3 MOLT-4 Investigative [1]
Astrocytoma DC2SGLA SNB-19 Investigative [1]
Glioma DCYYMBG SF-539 Investigative [1]
Colon carcinoma DCUIGXT KM12 Investigative [13]
Invasive ductal carcinoma DC3YSO9 T-47D Investigative [13]
Amelanotic melanoma DCNC60R MDA-MB-435 Investigative [14]
High grade ovarian serous adenocarcinoma DC0WG0B NCI\\/ADR-RES Investigative [14]
Lung adenocarcinoma DCY35VT NCI-H522 Investigative [14]
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⏷ Show the Full List of 8 DrugCom(s)

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 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 Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
5 Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703.
6 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.
7 Lonsurf, INN-trifluridine/tipiracil.
8 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.
9 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.
10 Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
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 Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019 Feb 27;24(5):841. doi: 10.3390/molecules24050841.
13 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
14 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.