General Information of Drug Combination (ID: DCPVB08)

Drug Combination Name
Idarubicin MK-1775
Indication
Disease Entry Status REF
Non small cell carcinoma Investigative [1]
Component Drugs Idarubicin   DMM0XGL MK-1775   DM3WDZ5
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SKMES1
Zero Interaction Potency (ZIP) Score: 26.34
Bliss Independence Score: 26.56
Loewe Additivity Score: 13.81
LHighest Single Agent (HSA) Score: 30.7

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Idarubicin
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [2]
Acute myeloid leukaemia 2A60 Approved [3]
Adult acute monocytic leukemia N.A. Approved [2]
Childhood acute megakaryoblastic leukemia N.A. Approved [2]
Leukemia N.A. Approved [2]
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 [7]
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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 [8]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
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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 [10]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [10]
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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 [6]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [11]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Increases Activity [6]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [12]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Activity [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [13]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Decreases Activity [6]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [14]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Activity [6]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of MK-1775
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 2 [4]
Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
MK-1775 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Wee1-like protein kinase (WEE1) TTJFOAL WEE1_HUMAN Inhibitor [16]
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MK-1775 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Phosphorylation [15]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Response To Substance [15]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour DCNCQMG ES2 Investigative [17]
Breast and ovarian cancer syndrome DCNBZAE UWB1289 Investigative [18]
Breast and ovarian cancer syndrome DCESJGB UWB1289+BRCA1 Investigative [18]
Breast carcinoma DCQXID2 OCUBM Investigative [18]
Carcinoma DC1U2QD OV90 Investigative [18]
Carcinoma DCEK5FD EFM192B Investigative [18]
Carcinoma DCPQH4N MDAMB436 Investigative [18]
Colon adenocarcinoma DC1Z1AK LOVO Investigative [18]
Invasive ductal carcinoma DCVDCXG T-47D Investigative [18]
Adenocarcinoma DCX6RFQ OVCAR3 Investigative [1]
Adenocarcinoma DC28HEO A427 Investigative [1]
Adenocarcinoma DCTM16L NCIH1650 Investigative [1]
Adenocarcinoma DCUD797 NCIH2122 Investigative [1]
Adenocarcinoma DCJGDUJ NCIH23 Investigative [1]
Adenocarcinoma DCJH09S COLO320DM Investigative [1]
Adenocarcinoma DCTU7Z1 SW-620 Investigative [1]
Amelanotic melanoma DCFWILX A2058 Investigative [1]
Large cell lung carcinoma DCWEZ0T NCI-H460 Investigative [1]
Malignant melanoma DCBGW24 A375 Investigative [1]
Malignant melanoma DCHA3Z6 RPMI7951 Investigative [1]
Malignant melanoma DC4PRQ1 UACC62 Investigative [1]
Mesothelioma DCT4OGF MSTO Investigative [1]
Ovarian endometrioid adenocarcinoma DCWYB3D A2780 Investigative [1]
Ovarian serous cystadenocarcinoma DCK1LH4 SK-OV-3 Investigative [1]
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⏷ Show the Full List of 24 DrugCom(s)

References

1 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.
2 Idarubicin 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: 7083).
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: 7702).
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 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.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
9 Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
10 In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
11 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.
12 The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
13 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.
14 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.
15 Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin Cancer Res. 2014 Aug 15;20(16):4274-88. doi: 10.1158/1078-0432.CCR-13-2858.
16 A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
17 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.
18 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.