Details of the Drug Combination

General Information of Drug Combination (ID: DCLZDIY)

Drug Combination Name
NITD609 Bumetanide
Indication
Disease Entry Status REF
Hepatoblastoma Investigative [1]
Component Drugs NITD609   DMQHBSX Bumetanide   DMRV7H0
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HB3
Zero Interaction Potency (ZIP) Score: 9.043
Bliss Independence Score: 6.191
Loewe Additivity Score: 4.329
LHighest Single Agent (HSA) Score: 3.752

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of NITD609
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Phase 2 [2]
NITD609 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated potassium channel Kv11.1 (KCNH2) TTQ6VDM KCNH2_HUMAN Inhibitor [5]
Adenosine A3 receptor (ADORA3) TTJFY5U AA3R_HUMAN Inhibitor [5]
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Indication(s) of Bumetanide
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [3]
Edema MG29 Approved [4]
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)

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 ClinicalTrials.gov (NCT01836458) A Study to Find the Minimum Inhibitory Concentration of KAE609 in Adult Male Patients With P. Falciparum Monoinfection. U.S. National Institutes of Health.
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: 4837).
4 Bumetanide FDA Label
5 Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010 Sep 3;329(5996):1175-80.
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.