General Information of Drug Combination (ID: DC5JKS7)

Drug Combination Name
AKB-6548 Furosemide
Indication
Disease Entry Status REF
Drug Interaction Potentiation Phase 1 [1]
Component Drugs AKB-6548   DM2EJM3 Furosemide   DMMQ8ZG
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of AKB-6548
Disease Entry ICD 11 Status REF
Anaemia 3A90 Phase 3 [2]
AKB-6548 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HIF-prolyl hydroxylase (HPH) TTJQFBG NOUNIPROTAC Modulator [5]
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Indication(s) of Furosemide
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [3]
Edema MG29 Approved [4]
Renal hypoplasia N.A. Approved [4]
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]
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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]
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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]
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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]
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⏷ Show the Full List of 15 DOT(s)

References

1 ClinicalTrials.gov (NCT03801759) Drug-Drug Interaction Study of Vadadustat With Digoxin, Adefovir and Furosemide
2 ClinicalTrials.gov (NCT03242967) Study to Evaluate Three Times Per Week (TIW) Oral Dosing of Vadadustat for Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (TRILOGY). 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: 4839).
4 Furosemide FDA Label
5 DOI: 10.1038/nrd4422
6 Markers of electrophilic stress caused by chemically reactive metabolites in human hepatocytes. Drug Metab Dispos. 2008 May;36(5):816-23.
7 Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. J Biol Chem. 2004 Jul 2;279(27):28320-9. doi: 10.1074/jbc.M401396200. Epub 2004 Apr 26.
8 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
9 Update of diuretics in the treatment of hypertension. Am J Ther. 2007 Mar-Apr;14(2):154-60.
10 Peptide transporter substrate identification during permeability screening in drug discovery: comparison of transfected MDCK-hPepT1 cells to Caco-2 cells. Arch Pharm Res. 2007 Apr;30(4):507-18.
11 Interactions of human organic anion transporters with diuretics. J Pharmacol Exp Ther. 2004 Mar;308(3):1021-9.
12 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
13 Effects of cytochrome P450 inducers and inhibitors on the pharmacokinetics of intravenous furosemide in rats: involvement of CYP2C11, 2E1, 3A1 and 3A2 in furosemide metabolism. J Pharm Pharmacol. 2009 Jan;61(1):47-54.
14 Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide. Eur J Clin Pharmacol. 1996;49(5):393-6.
15 Inhibition profiling of human carbonic anhydrase II by high-throughput screening of structurally diverse, biologically active compounds. J Biomol Screen. 2006 Oct;11(7):782-91.
16 Endogenous bradykinin and the renin and pressor responses to furosemide in humans. J Pharmacol Exp Ther. 2000 Nov;295(2):644-8.
17 Secondary pulmonary hypertension: haemodynamic effects of torasemide versus furosemide. Clin Drug Investig. 2008;28(1):17-26. doi: 10.2165/00044011-200828010-00003.
18 [Effects of 4-hour erect posture and furosemide on the blood level of atrial natriuretic peptide in patients with primary arterial hypertension]. Przegl Lek. 1990;47(3):332-4.
19 Antihypertensive drugs clonidine, diazoxide, hydralazine and furosemide regulate the production of cytokines by placentas and peripheral blood mononuclear cells in normal pregnancy. J Hypertens. 2006 May;24(5):915-22. doi: 10.1097/01.hjh.0000222762.84605.03.
20 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.
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.
22 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.
23 A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
24 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.