Details of the Drug Combination

General Information of Drug Combination (ID: DC4IQ3M)

Drug Combination Name
Losartan Leucovorin
Indication
Disease Entry Status REF
Pancreatic Cancer Phase 2 [1]
Component Drugs Losartan   DM72JXH Leucovorin   DMUAZWG
Small molecular drug 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 Losartan
Disease Entry ICD 11 Status REF
Diabetic kidney disease GB61.Z Approved [2]
Hypertension BA00-BA04 Approved [3]
Prediabetes syndrome N.A. Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
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 [6]
HUMAN type-1 angiotensin II receptor (AGTR1) TTPKMXQ AGTR1_HUMAN Blocker [7]
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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 [8]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [9]
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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 [10]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [11]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [10]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [12]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [13]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [13]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [13]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DEL5N6Y UD110_HUMAN Metabolism [13]
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⏷ Show the Full List of 8 DME(s)
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 [14]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases ADR [14]
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Indication(s) of Leucovorin
Disease Entry ICD 11 Status REF
Colon adenocarcinoma N.A. Approved [5]
Pervasive developmental disorder 6A00-6A0Z Approved [5]
Rectal adenocarcinoma 2B92 Approved [5]
Rectum mucinous adenocarcinoma N.A. Approved [5]
Colon cancer 2B90.Z Investigative [5]
Colon mucinous adenocarcinoma N.A. Investigative [5]
Megaloblastic anemia N.A. Investigative [5]
Methotrexate toxicity N.A. Investigative [5]
Leucovorin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [15]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [16]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [17]
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References

1 ClinicalTrials.gov (NCT01821729) Proton w/FOLFIRINOX-Losartan for Pancreatic Cancer
2 Losartan FDA Label
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: 590).
4 ClinicalTrials.gov (NCT04343001) Coronavirus Response - Active Support for Hospitalised Covid-19 Patients. U.S. National Institutes of Health.
5 Leucovorin FDA Label
6 Radioligand binding assays: application of [(125)I]angiotensin II receptor binding. Methods Mol Biol. 2009;552:131-41.
7 Controversies of renin-angiotensin system inhibition during the COVID-19 pandemic. Nat Rev Nephrol. 2020 Apr 3.
8 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.
9 High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
10 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
11 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.
12 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.
13 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.
14 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.
15 Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 2003 Jul 15;63(14):4048-54.
16 Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32.
17 Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50.