General Information of Drug Combination (ID: DCURT5Q)

Drug Combination Name
Metyrosine Spironolactone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Metyrosine   DMBYCU0 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: 13.57
Bliss Independence Score: 13.57
Loewe Additivity Score: 16.06
LHighest Single Agent (HSA) Score: 16.06

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Metyrosine
Disease Entry ICD 11 Status REF
Pheochromocytoma 5A75 Approved [2]
Metyrosine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tyrosine 3-monooxygenase (TH) TTUHP71 TY3H_HUMAN Binder [6]
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Indication(s) of Spironolactone
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [3]
Congestive heart failure BD10 Approved [4]
Edema MG29 Approved [3]
Hyperaldosteronism 5A72 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [5]
Spironolactone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Mineralocorticoid receptor (MR) TT26PHO MCR_HUMAN Modulator [7]
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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 [8]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Activity [9]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [10]
Serine/threonine-protein kinase Sgk1 (SGK1) OT301T1U SGK1_HUMAN Increases Expression [11]
Tissue-type plasminogen activator (PLAT) OTQPDNAB TPA_HUMAN Increases Expression [12]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Increases Expression [13]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Expression [14]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [15]
Collagen alpha-1(III) chain (COL3A1) OTT1EMLM CO3A1_HUMAN Decreases Expression [14]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Increases Expression [16]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Decreases Expression [12]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [17]
Mineralocorticoid receptor (NR3C2) OT0F2V2Z MCR_HUMAN Increases Activity [18]
Myb-related protein A (MYBL1) OTBJMC2P MYBA_HUMAN Increases Expression [11]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Affects Binding [19]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Decreases Expression [14]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [20]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [20]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Increases Expression [11]
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Response To Substance [21]
Serum paraoxonase/lactonase 3 (PON3) OT80W9TA PON3_HUMAN Increases Hydrolysis [22]
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⏷ Show the Full List of 21 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 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: 6956).
3 Spironolactone FDA Label
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: 2875).
5 Spironolactone in Covid-19 Induced ARDS
6 Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. Hypertension. 1991 Jul;18(1):1-8.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8 Receptor-dependent regulation of the CYP3A4 gene. Toxicology. 2002 Dec 27;181-182:199-202.
9 Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78.
10 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
11 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.
12 Effect of spironolactone on impaired fibrinolysis of hypertensive patients. Kidney Blood Press Res. 2002;25(4):260-4. doi: 10.1159/000066348.
13 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.
14 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.
15 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.
16 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.
17 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.
18 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.
19 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.
20 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.
21 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.
22 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.