General Information of Drug Combination (ID: DC658LJ)

Drug Combination Name
GSK525762 Idarubicin
Indication
Disease Entry Status REF
Glioblastoma? Investigative [1]
Component Drugs GSK525762   DMPAWBN Idarubicin   DMM0XGL
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: T98G
Zero Interaction Potency (ZIP) Score: 53.91
Bliss Independence Score: 53.91
Loewe Additivity Score: 51.23
LHighest Single Agent (HSA) Score: 51.23

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of GSK525762
Disease Entry ICD 11 Status REF
Haematological malignancy 2B33.Y Phase 1 [2]
Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
GSK525762 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bromodomain-containing protein 4 (BRD4) TTRA6BO BRD4_HUMAN Modulator [7]
Bromodomain and extraterminal domain protein (BET) TTE4BSY NOUNIPROTAC Inhibitor [2]
------------------------------------------------------------------------------------
GSK525762 Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Expression [8]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Expression [9]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Decreases Expression [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [9]
Protein-lysine 6-oxidase (LOX) OT1C2HIU LYOX_HUMAN Decreases Expression [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [10]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [10]
Carbonic anhydrase 9 (CA9) OTNA51XT CAH9_HUMAN Decreases Expression [6]
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) OT25JBA3 F263_HUMAN Increases Expression [6]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Decreases Expression [9]
Endothelial PAS domain-containing protein 1 (EPAS1) OTRE3O8U EPAS1_HUMAN Increases Expression [6]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 DOT(s)
Indication(s) of Idarubicin
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [4]
Acute myeloid leukaemia 2A60 Approved [5]
Adult acute monocytic leukemia N.A. Approved [4]
Childhood acute megakaryoblastic leukemia N.A. Approved [4]
Leukemia N.A. Approved [4]
Idarubicin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Modulator [12]
------------------------------------------------------------------------------------
Idarubicin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [13]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [14]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [14]
------------------------------------------------------------------------------------
Idarubicin Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [15]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [15]
------------------------------------------------------------------------------------
Idarubicin Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Activity [11]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [16]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Increases Activity [11]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [17]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Activity [11]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [18]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Decreases Activity [11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [19]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Activity [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 9 DOT(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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 7033).
4 Idarubicin FDA Label
5 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: 7083).
6 The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer. Oncogene. 2017 Jan 5;36(1):122-132. doi: 10.1038/onc.2016.184. Epub 2016 Jun 13.
7 Targeting bromodomains: epigenetic readers of lysine acetylation.Nat Rev Drug Discov.2014 May;13(5):337-56.
8 Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem. 2011 Jun 9;54(11):3827-38.
9 An epigenomic approach to therapy for tamoxifen-resistant breast cancer. Cell Res. 2014 Jul;24(7):809-19. doi: 10.1038/cr.2014.71. Epub 2014 May 30.
10 MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 2016 Apr;23(4):335-47. doi: 10.1530/ERC-15-0322. Epub 2016 Feb 24.
11 Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
12 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
13 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
14 Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
15 In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
16 A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
17 The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
18 The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts. Cell Mol Biol Lett. 2008;13(2):182-94. doi: 10.2478/s11658-007-0045-7. Epub 2008 Apr 10.
19 Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.