General Information of Drug Combination (ID: DCSN04H)

Drug Combination Name
AKB-6548 Digoxin
Indication
Disease Entry Status REF
Drug Interaction Potentiation Phase 1 [1]
Component Drugs AKB-6548   DM2EJM3 Digoxin   DMQCTIH
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 Digoxin
Disease Entry ICD 11 Status REF
Arrhythmia BC9Z Approved [3]
Atrial fibrillation BC81.3 Approved [4]
Chronic heart failure BD1Z Approved [4]
Congestive cardiac insufficiency BD1Z Approved [3]
Heart failure BD10-BD13 Approved [3]
Digoxin Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sodium/potassium-transporting ATPase (SPT ATPase) TTQ38E9 AT1A1_HUMAN; AT1A2_HUMAN; AT1A3_HUMAN; AT1B1_HUMAN; AT1B2_HUMAN; AT1B3_HUMAN Inhibitor [7]
Organic anion transporter M1 (SLCO4C1) TTACFNR SO4C1_HUMAN Modulator [8]
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Digoxin Interacts with 7 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
Multidrug resistance protein 3 (ABCB4) DTZRMK5 MDR3_HUMAN Substrate [10]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [11]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [12]
Organic solute transporter subunit alpha (SLC51A) DTMEQ32 OSTA_HUMAN Substrate [13]
Organic solute transporter subunit beta (SLC51B) DT1V9AJ OSTB_HUMAN Substrate [13]
Organic anion transporting polypeptide 4C1 (SLCO4C1) DTY0QMU SO4C1_HUMAN Substrate [14]
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⏷ Show the Full List of 7 DTP(s)
Digoxin Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [15]
Cardiac glycoside reductase 1 (cgr1) DE84PFW CGR1_EGGLE Metabolism [16]
Cardiac glycoside reductase 2 (cgr2) DE9VSLW CGR2_EGGLE Metabolism [16]
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Digoxin Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [17]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases ADR [18]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Decreases Expression [6]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [19]
C-C motif chemokine 4 (CCL4) OT6B8P25 CCL4_HUMAN Decreases Expression [6]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Decreases Expression [6]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Expression [6]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [20]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [21]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Activity [17]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Activity [22]
Sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1) OTCJ458Q AT1A1_HUMAN Increases ADR [18]
p21 protein (HRAS) OTFYE6AJ P78460_HUMAN Increases ADR [18]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases ADR [18]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Response To Substance [23]
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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: 4726).
4 Digoxin FDA Label
5 DOI: 10.1038/nrd4422
6 Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents. Leuk Res. 2010 Jul;34(7):917-24. doi: 10.1016/j.leukres.2009.12.002. Epub 2010 Feb 8.
7 Fab antibody fragments: some applications in clinical toxicology. Drug Saf. 2004;27(14):1115-33.
8 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. (Target id: 1227).
9 MDR1 function is sensitive to the phosphorylation state of myosin regulatory light chain. Biochem Biophys Res Commun. 2010 Jul 16;398(1):7-12.
10 MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J Biol Chem. 2000 Aug 4;275(31):23530-9.
11 Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
12 Drug Interactions in Infectious Diseases.
13 Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta. J Biol Chem. 2003 Jul 25;278(30):27473-82.
14 Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74.
15 Omeprazole-associated digoxin toxicity. South Med J. 2007 Apr;100(4):400-2.
16 Mechanistic insight into digoxin inactivation by Eggerthella lenta augments our understanding of its pharmacokinetics. Gut Microbes. 2014 Mar-Apr;5(2):233-8.
17 Digoxin and ouabain induce P-glycoprotein by activating calmodulin kinase II and hypoxia-inducible factor-1alpha in human colon cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):385-92. doi: 10.1016/j.taap.2009.07.026. Epub 2009 Jul 30.
18 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.
19 Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay. Arch Toxicol. 2018 Jun;92(6):2043-2054. doi: 10.1007/s00204-018-2199-7. Epub 2018 Mar 29.
20 Chronic digoxin toxicity and significantly elevated BNP levels in the presence of mild heart failure. Am J Emerg Med. 2005 Jul;23(4):561-2. doi: 10.1016/j.ajem.2004.10.009.
21 Intracellular potassium stabilizes human ether--go-go-related gene channels for export from endoplasmic reticulum. Mol Pharmacol. 2009 Apr;75(4):927-37. doi: 10.1124/mol.108.053793. Epub 2009 Jan 12.
22 Human breast cancer resistance protein: interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine. J Pharmacol Exp Ther. 2005 Jan;312(1):144-52. doi: 10.1124/jpet.104.073916. Epub 2004 Sep 13.
23 Insulin interacts directly with Na?/K?ATPase and protects from digoxin toxicity. Toxicology. 2012 Sep 4;299(1):1-9. doi: 10.1016/j.tox.2012.04.013. Epub 2012 May 4.