General Information of Drug Combination (ID: DCT1PRG)

Drug Combination Name
Bumetanide Iloprost
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Bumetanide   DMRV7H0 Iloprost   DMVPZBE
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: 9.67
Bliss Independence Score: 9.67
Loewe Additivity Score: 21.06
LHighest Single Agent (HSA) Score: 21.08

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Bumetanide
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [2]
Edema MG29 Approved [3]
Bumetanide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Solute carrier family 12 member 1 (SLC12A1) TTS087L S12A1_HUMAN Blocker [6]
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Bumetanide Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [7]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [8]
Organic anion transporter 4 (SLC22A11) DT06JWZ S22AB_HUMAN Substrate [8]
Thiazide-sensitive sodium-chloride cotransporter (SLC12A3) DT6MDC9 S12A3_HUMAN Substrate [9]
Monocarboxylate transporter 6 (SLC16A5) DT3I124 MOT6_HUMAN Substrate [10]
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Bumetanide Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier family 22 member 7 (SLC22A7) OTKTNH1W S22A7_HUMAN Increases Transport [7]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Expression [11]
Cystic fibrosis transmembrane conductance regulator (CFTR) OT6B22QH CFTR_HUMAN Decreases Activity [12]
HLA class I histocompatibility antigen, alpha chain G (HLA-G) OTMLK1KN HLAG_HUMAN Affects Expression [13]
Solute carrier family 12 member 2 (SLC12A2) OT3ZJ3LH S12A2_HUMAN Decreases Activity [14]
Sodium-dependent phosphate transport protein 4 (SLC17A3) OTMJWIBM NPT4_HUMAN Affects Transport [15]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Increases Transport [16]
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⏷ Show the Full List of 7 DOT(s)
Indication(s) of Iloprost
Disease Entry ICD 11 Status REF
Pulmonary arterial hypertension BB01.0 Approved [4]
Pulmonary hypertension BB01 Approved [5]
Systemic sclerosis 4A42 Approved [5]
Iloprost Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Prostaglandin E2 receptor EP2 (PTGER2) TT1ZAVI PE2R2_HUMAN Agonist [17]
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Iloprost Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporting polypeptide 2A1 (SLCO2A1) DT021JD SO2A1_HUMAN Substrate [18]
Organic anion transporting polypeptide 3A1 (SLCO3A1) DTVNRXW SO3A1_HUMAN Substrate [19]
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Iloprost Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Angiopoietin-2 (ANGPT2) OTEQK65P ANGP2_HUMAN Increases Expression [20]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [21]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Expression [21]
Fibroblast growth factor 2 (FGF2) OT7YUJ9F FGF2_HUMAN Increases Expression [20]
L-selectin (SELL) OT6RAJZR LYAM1_HUMAN Decreases Expression [21]
DNA-binding protein inhibitor ID-1 (ID1) OTKGNZN5 ID1_HUMAN Increases Expression [22]
Prostacyclin receptor (PTGIR) OTWTABYM PI2R_HUMAN Affects Binding [23]
Angiopoietin-1 (ANGPT1) OTVZ1NG3 ANGP1_HUMAN Increases Expression [20]
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⏷ Show the Full List of 8 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: 4837).
3 Bumetanide 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: 1966).
5 Iloprost FDA Label
6 Nerve Terminal GABAA Receptors Activate Ca2+/Calmodulin-dependent Signaling to Inhibit Voltage-gated Ca2+ Influx and Glutamate Release. J Biol Chem. 2009 Mar 27;284(13):8726-37.
7 Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8.
8 Interactions of human organic anion transporters with diuretics. J Pharmacol Exp Ther. 2004 Mar;308(3):1021-9.
9 Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9.
10 Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of Monocarboxylate Transporter 6. Mol Pharm. 2017 Sep 5;14(9):2930-2936.
11 Dosage dependent hormonal counter regulation to combination therapy in patients with left ventricular dysfunction. J Clin Pharm Ther. 2006 Apr;31(2):139-47. doi: 10.1111/j.1365-2710.2006.00606.x.
12 Effects of a new cystic fibrosis transmembrane conductance regulator inhibitor on Cl- conductance in human sweat ducts. Exp Physiol. 2004 Jul;89(4):417-25. doi: 10.1113/expphysiol.2003.027003. Epub 2004 May 6.
13 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
14 Azosemide is more potent than bumetanide and various other loop diuretics to inhibit the sodium-potassium-chloride-cotransporter human variants hNKCC1A and hNKCC1B. Sci Rep. 2018 Jun 29;8(1):9877. doi: 10.1038/s41598-018-27995-w.
15 Functional analysis of human sodium-phosphate transporter 4 (NPT4/SLC17A3) polymorphisms. J Pharmacol Sci. 2011;115(2):249-53. doi: 10.1254/jphs.10228sc. Epub 2011 Jan 26.
16 Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96.
17 Exploration of prostanoid receptor subtype regulating estradiol and prostaglandin E2 induction of spinophilin in developing preoptic area neurons. Neuroscience. 2007 May 25;146(3):1117-27.
18 Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J Clin Invest. 1996 Sep 1;98(5):1142-9.
19 Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97.
20 Prostacyclin receptor up-regulates the expression of angiogenic genes in human endometrium via cross talk with epidermal growth factor Receptor and the extracellular signaling receptor kinase 1/2 pathway. Endocrinology. 2006 Apr;147(4):1697-705. doi: 10.1210/en.2005-1073. Epub 2005 Dec 22.
21 The response of skin perfusion and of rheological and immunological variables to intravenous prostanoid administration in Raynaud's phenomenon secondary to collagenosis. Vasa. 2005 Nov;34(4):243-9. doi: 10.1024/0301-1526.34.4.243.
22 Smad-dependent and smad-independent induction of id1 by prostacyclin analogues inhibits proliferation of pulmonary artery smooth muscle cells in vitro and in vivo. Circ Res. 2010 Jul 23;107(2):252-62. doi: 10.1161/CIRCRESAHA.109.209940. Epub 2010 Jun 3.
23 Investigation of a functional requirement for isoprenylation by the human prostacyclin receptor. Eur J Biochem. 2002 Mar;269(6):1714-25. doi: 10.1046/j.1432-1327.2002.02817.x.