General Information of Drug Combination (ID: DCIEEOX)

Drug Combination Name
Idarubicin Spironolactone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Idarubicin   DMM0XGL Spironolactone   DM2AQ5N
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 10.19
Bliss Independence Score: 10.19
Loewe Additivity Score: 18.02
LHighest Single Agent (HSA) Score: 18.02

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 [8]
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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 [9]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [10]
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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 [11]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [11]
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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 [7]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [12]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Increases Activity [7]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [13]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Activity [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [14]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Decreases Activity [7]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [15]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Activity [7]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Spironolactone
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [4]
Congestive heart failure BD10 Approved [5]
Edema MG29 Approved [4]
Hyperaldosteronism 5A72 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [6]
Spironolactone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Mineralocorticoid receptor (MR) TT26PHO MCR_HUMAN Modulator [8]
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Spironolactone Interacts with 21 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [16]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Activity [17]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [18]
Serine/threonine-protein kinase Sgk1 (SGK1) OT301T1U SGK1_HUMAN Increases Expression [19]
Tissue-type plasminogen activator (PLAT) OTQPDNAB TPA_HUMAN Increases Expression [20]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Increases Expression [21]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Expression [22]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [23]
Collagen alpha-1(III) chain (COL3A1) OTT1EMLM CO3A1_HUMAN Decreases Expression [22]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Increases Expression [24]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Decreases Expression [20]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [25]
Mineralocorticoid receptor (NR3C2) OT0F2V2Z MCR_HUMAN Increases Activity [26]
Myb-related protein A (MYBL1) OTBJMC2P MYBA_HUMAN Increases Expression [19]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Affects Binding [27]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Decreases Expression [22]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [28]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [28]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Increases Expression [19]
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Response To Substance [29]
Serum paraoxonase/lactonase 3 (PON3) OT80W9TA PON3_HUMAN Increases Hydrolysis [30]
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⏷ Show the Full List of 21 DOT(s)

References

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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 Spironolactone 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: 2875).
6 Spironolactone in Covid-19 Induced ARDS
7 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.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
10 Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
11 In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
12 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.
13 The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
14 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.
15 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.
16 Receptor-dependent regulation of the CYP3A4 gene. Toxicology. 2002 Dec 27;181-182:199-202.
17 Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78.
18 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
19 A Gene Expression Biomarker Identifies Chemical Modulators of Estrogen Receptor in an MCF-7 Microarray Compendium. Chem Res Toxicol. 2021 Feb 15;34(2):313-329. doi: 10.1021/acs.chemrestox.0c00243. Epub 2021 Jan 6.
20 Effect of spironolactone on impaired fibrinolysis of hypertensive patients. Kidney Blood Press Res. 2002;25(4):260-4. doi: 10.1159/000066348.
21 Amiloride, spironolactone, and potassium chloride in thiazide-treated hypertensive patients. Clin Pharmacol Ther. 1980 Apr;27(4):533-43. doi: 10.1038/clpt.1980.75.
22 Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol. 2001 Apr;37(5):1228-33. doi: 10.1016/s0735-1097(01)01116-0.
23 Spironolactone induces apoptosis in human mononuclear cells. Association between apoptosis and cytokine suppression. Apoptosis. 2006 Apr;11(4):573-9. doi: 10.1007/s10495-006-4919-3.
24 Evaluation of an imaging-based in vitro screening platform for estrogenic activity with OECD reference chemicals. Toxicol In Vitro. 2022 Jun;81:105348. doi: 10.1016/j.tiv.2022.105348. Epub 2022 Mar 18.
25 Pregnane X receptor mediates the induction of P-glycoprotein by spironolactone in HepG2 cells. Toxicology. 2011 Jul 11;285(1-2):18-24. doi: 10.1016/j.tox.2011.03.015. Epub 2011 Apr 1.
26 The human mineralocorticoid receptor only partially differentiates between different ligands after expression in fission yeast. FEMS Yeast Res. 2005 Apr;5(6-7):627-33. doi: 10.1016/j.femsyr.2004.12.007.
27 Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals. Toxicology. 2004 Feb 15;195(2-3):177-86. doi: 10.1016/j.tox.2003.09.012.
28 Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease. Toxicol Sci. 2012 Oct;129(2):346-62. doi: 10.1093/toxsci/kfs208. Epub 2012 Jun 14.
29 Clinical and biochemical effects of spironolactone administered once daily in primary hypertension. Multicenter Sweden study. Hypertension. 1980 Sep-Oct;2(5):672-9. doi: 10.1161/01.hyp.2.5.672.
30 Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res. 2005 Jun;46(6):1239-47. doi: 10.1194/jlr.M400511-JLR200. Epub 2005 Mar 16.