Details of the Drug Combination

General Information of Drug Combination (ID: DCDX1HD)

Drug Combination Name
Indazole derivative 5 Pralatrexate
Indication
Disease Entry Status REF
Adult T acute lymphoblastic leukemia Investigative [1]
Component Drugs Indazole derivative 5   DMM1I8R Pralatrexate   DMAO80I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: MOLT-4
Zero Interaction Potency (ZIP) Score: 0.35
Bliss Independence Score: 6.65
Loewe Additivity Score: 6.96
LHighest Single Agent (HSA) Score: 6.93

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 Pralatrexate
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [2]
Peripheral T-cell lymphoma 2A90.C Approved [2]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [3]
Pralatrexate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Polypeptide deformylase (PDF) TT9SL3Q DEFM_HUMAN Inhibitor [5]
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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 [6]
Proton-coupled folate transporter (SLC46A1) DTDJEMI PCFT_HUMAN Substrate [6]
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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 [7]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Childhood T acute lymphoblastic leukemia DC6NUZ6 CCRF-CEM Investigative [1]
Clear cell renal cell carcinoma DCFL9OB TK-10 Investigative [1]
Adenocarcinoma DCEYO90 HCT-15 Investigative [8]
Adenocarcinoma DCRLRPD HCC-2998 Investigative [8]
High grade ovarian serous adenocarcinoma DC0CLGE OVCAR-4 Investigative [8]
Lung adenocarcinoma DCPTMXH HOP-62 Investigative [8]
Minimally invasive lung adenocarcinoma DC9TAXZ NCI-H322M Investigative [8]
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⏷ Show the Full List of 7 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 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).
3 Pralatrexate FDA Label
4 Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
5 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
6 Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.
7 Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23.
8 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.