Details of the Drug Combination

General Information of Drug Combination (ID: DCQ6FPL)

• Drug Combination Name: Furosemide + Bumetanide
• Indication: Heart Failure, Congestive; Status: Phase 4 [1]
• Component Drugs:
  Furosemide (DMMQ8ZG): Small molecular drug
  Bumetanide (DMRV7H0): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Furosemide

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[2]
Edema	MG29	Approved	[3]
Renal hypoplasia	N.A.	Approved	[3]

Furosemide 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	[9]

Furosemide Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[10]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[11]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[11]

Furosemide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[12]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[13]

Furosemide Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Decreases Activity	[14]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Decreases Activity	[15]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[16]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Increases Expression	[17]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Decreases Expression	[18]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[19]
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Affects Expression	[20]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[21]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[19]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Decreases Secretion	[19]
Solute carrier family 12 member 2 (SLC12A2)	OT3ZJ3LH	S12A2_HUMAN	Decreases Activity	[22]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[23]
ATP-binding cassette sub-family C member 4 (ABCC4)	OTO27PAL	MRP4_HUMAN	Increases Transport	[24]
Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)	OTQF5ZAK	PTH1R_HUMAN	Increases ADR	[8]
Lipoprotein lipase (LPL)	OTTW0267	LIPL_HUMAN	Increases ADR	[8]

Indication(s) of Bumetanide

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[4]
Edema	MG29	Approved	[5]

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	[25]

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	[26]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[11]
Organic anion transporter 4 (SLC22A11)	DT06JWZ	S22AB_HUMAN	Substrate	[11]
Thiazide-sensitive sodium-chloride cotransporter (SLC12A3)	DT6MDC9	S12A3_HUMAN	Substrate	[27]
Monocarboxylate transporter 6 (SLC16A5)	DT3I124	MOT6_HUMAN	Substrate	[28]

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	[26]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Expression	[29]
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Decreases Activity	[30]
HLA class I histocompatibility antigen, alpha chain G (HLA-G)	OTMLK1KN	HLAG_HUMAN	Affects Expression	[20]
Solute carrier family 12 member 2 (SLC12A2)	OT3ZJ3LH	S12A2_HUMAN	Decreases Activity	[22]
Sodium-dependent phosphate transport protein 4 (SLC17A3)	OTMJWIBM	NPT4_HUMAN	Affects Transport	[31]
ATP-binding cassette sub-family C member 4 (ABCC4)	OTO27PAL	MRP4_HUMAN	Increases Transport	[24]

References

• [1] ClinicalTrials.gov (NCT06218199) Diuretics vs. Afterload Reduction for Treatment of HeartLogic Alerts
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• [3] Furosemide 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: 4837).
• [5] Bumetanide FDA Label
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• [21] Bucolome, a potent binding inhibitor for furosemide, alters the pharmacokinetics and diuretic effect of furosemide: potential for use of bucolome to restore diuretic response in nephrotic syndrome. Drug Metab Dispos. 2005 Apr;33(4):596-602. doi: 10.1124/dmd.104.002782. Epub 2005 Jan 7.
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