Details of the Drug Combination

General Information of Drug Combination (ID: DCDIPL0)

Drug Combination Name
FORMESTANE Pralatrexate
Indication
Disease Entry Status REF
Childhood T acute lymphoblastic leukemia Investigative [1]
Component Drugs FORMESTANE   DMWIDJK Pralatrexate   DMAO80I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: CCRF-CEM
Zero Interaction Potency (ZIP) Score: 5.56
Bliss Independence Score: 8.41
Loewe Additivity Score: 2.34
LHighest Single Agent (HSA) Score: 1.99

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of FORMESTANE
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Withdrawn from market [2]
FORMESTANE Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [5]
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FORMESTANE Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Adenylate kinase isoenzyme 1 (AK1) OT614AR3 KAD1_HUMAN Increases ADR [6]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [7]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) OT6EBDHM DHB1_HUMAN Decreases Activity [8]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Increases Expression [9]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Increases Expression [9]
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Indication(s) of Pralatrexate
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [3]
Peripheral T-cell lymphoma 2A90.C Approved [3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [4]
Pralatrexate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Polypeptide deformylase (PDF) TT9SL3Q DEFM_HUMAN Inhibitor [10]
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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 [11]
Proton-coupled folate transporter (SLC46A1) DTDJEMI PCFT_HUMAN Substrate [11]
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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 [12]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Cutaneous melanoma DCFRSRH SK-MEL-28 Investigative [1]
Glioma DCU1IYA SF-295 Investigative [1]
Glioma DCVGK60 SF-268 Investigative [1]
Large cell lung carcinoma DCXPSQ0 NCI-H460 Investigative [1]
Pleural epithelioid mesothelioma DC6SNWM NCI-H226 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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 6840).
4 Pralatrexate FDA Label
5 The taiwaniaquinoids: a review. J Nat Prod. 2010 Feb 26;73(2):284-98.
6 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
7 Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro. Toxicol In Vitro. 2000 Jun;14(3):227-34.
8 Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells. J Steroid Biochem Mol Biol. 2005 Apr;94(5):461-7.
9 Androgen- and estrogen-receptor mediated activities of 4-hydroxytestosterone, 4-hydroxyandrostenedione and their human metabolites in yeast based assays. Toxicol Lett. 2018 Aug;292:39-45. doi: 10.1016/j.toxlet.2018.04.026. Epub 2018 Apr 24.
10 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
11 Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.
12 Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23.