Details of the Drug Combination

General Information of Drug Combination (ID: DCATMLS)

• Drug Combination Name: Empagliflozin + Losartan
• Indication: Diabetes Mellitus, Type 2; Status: Phase 4 [1]
• Component Drugs:
  Empagliflozin (DMRF9YK): Small molecular drug
  Losartan (DM72JXH): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Empagliflozin

Disease Entry	ICD 11	Status	REF
Type-1 diabetes	5A10	Approved	[2]

Empagliflozin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium/glucose cotransporter 2 (SGLT2)	TTLWPVF	SC5A2_HUMAN	Modulator	[6]

Empagliflozin Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]

Empagliflozin Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A8 (UGT1A8)	DE2GB8N	UD18_HUMAN	Metabolism	[9]

Indication(s) of Losartan

Disease Entry	ICD 11	Status	REF
Diabetic kidney disease	GB61.Z	Approved	[3]
Hypertension	BA00-BA04	Approved	[4]
Prediabetes syndrome	N.A.	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[5]

Losartan Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiotensin II receptor type-1 (AGTR1)	TT8DBY3	AGTR1_HUMAN	Antagonist	[10]
HUMAN type-1 angiotensin II receptor (AGTR1)	TTPKMXQ	AGTR1_HUMAN	Blocker	[11]

Losartan Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[13]

Losartan Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[14]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[15]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[14]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[16]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[17]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[17]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[17]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[17]

Losartan Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Increases ADR	[18]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases ADR	[18]

References

• [1] ClinicalTrials.gov (NCT04238702) Renohemodynamic Effects of Combined empagliflOzin and LosARtan
• [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: 4754).
• [3] Losartan 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: 590).
• [5] ClinicalTrials.gov (NCT04343001) Coronavirus Response - Active Support for Hospitalised Covid-19 Patients. U.S. National Institutes of Health.
• [6] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [7] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [8] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
• [9] Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes. P T. 2015 Jun;40(6):364-8.
• [10] Radioligand binding assays: application of [(125)I]angiotensin II receptor binding. Methods Mol Biol. 2009;552:131-41.
• [11] Controversies of renin-angiotensin system inhibition during the COVID-19 pandemic. Nat Rev Nephrol. 2020 Apr 3.
• [12] Active transport of the angiotensin-II antagonist losartan and its main metabolite EXP 3174 across MDCK-MDR1 and caco-2 cell monolayers. Br J Pharmacol. 2000 Mar;129(6):1235-43.
• [13] High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
• [14] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [15] The human UDP-glucuronosyltransferase UGT1A3 is highly selective towards N2 in the tetrazole ring of losartan, candesartan, and zolarsartan. Biochem Pharmacol. 2008 Sep 15;76(6):763-72.
• [16] Drug-drug interaction between losartan and paclitaxel in human liver microsomes with different CYP2C8 genotypes. Basic Clin Pharmacol Toxicol. 2015 Jun;116(6):493-8.
• [17] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [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.