General Information of Drug Combination (ID: DC1E5J4)

Drug Combination Name
Fexofenadine Sulfasalazine
Indication
Disease Entry Status REF
Pharmacokinetics Phase 1 [1]
Component Drugs Fexofenadine   DM17ONX Sulfasalazine   DMICA9H
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 Fexofenadine
Disease Entry ICD 11 Status REF
Allergic rhinitis CA08.0 Approved [2]
Seasonal allergic rhinitis CA08.01 Approved [3]
Fexofenadine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Histamine H1 receptor (H1R) TTTIBOJ HRH1_HUMAN Antagonist [7]
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Fexofenadine Interacts with 6 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [9]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [10]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [11]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [12]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [13]
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⏷ Show the Full List of 6 DTP(s)
Fexofenadine Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Affects Response To Substance [14]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) OTOM3BUH SO1B3_HUMAN Increases Uptake [10]
C-C motif chemokine 22 (CCL22) OTT3QJC2 CCL22_HUMAN Decreases Expression [15]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Decreases Expression [16]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [16]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Decreases Expression [16]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [16]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [15]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [15]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [16]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Increases Uptake [10]
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⏷ Show the Full List of 11 DOT(s)
Indication(s) of Sulfasalazine
Disease Entry ICD 11 Status REF
Irritable bowel syndrome DD91.0 Approved [4]
Rheumatoid arthritis FA20 Approved [5]
Ulcerative colitis DD71 Approved [6]
Sulfasalazine Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
ATP-binding cassette transporter G2 (ABCG2) TTIMJ02 ABCG2_HUMAN Inhibitor [19]
Nuclear factor NF-kappa-B (NFKB) TTSXVID NFKB1_HUMAN; NFKB2_HUMAN; TF65_HUMAN; RELB_HUMAN; REL_HUMAN Activator [20]
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Sulfasalazine Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [21]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [22]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [23]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [24]
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Sulfasalazine Interacts with 12 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [25]
Azoreductase (azoR) DE5CAX1 A0A074IU04_STRSL Metabolism [26]
Azoreductase (azoR) DEGTKHL T0VG26_9ENTE Metabolism [27]
Azoreductase (azoR) DE3UF6Z A0A0P0ETC6_BACT4 Metabolism [27]
Azoreductase (azoR) DE6GHJ5 A0A0P0ETC6_BACT4 Metabolism [27]
Azoreductase (azoR) DEEISQ2 AZOR_ENTFA Metabolism [26]
Azoreductase (azoR) DEI2PC5 AZOR_CLOP1 Metabolism [26]
Azoreductase (azoR) DETEMAH A0A349MYB4_9LACO Metabolism [27]
Azoreductase (azoR) DEM1BHT A0A132Z973_ENTFC Metabolism [26]
Azoreductase (azoR) DEIKZOU A0A0P0ETC6_BACT4 Metabolism [28]
Azoreductase (azoR) DENLBG3 A0A0P0ETC6_BACT4 Metabolism [26]
Azoreductase (azoR) DEIHK8V A0A349MYB4_9LACO Metabolism [26]
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⏷ Show the Full List of 12 DME(s)
Sulfasalazine Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Methylation [29]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Decreases Expression [17]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) OTQ4W7MT TR11B_HUMAN Increases Secretion [30]
Tumor necrosis factor ligand superfamily member 11 (TNFSF11) OTJEPKEQ TNF11_HUMAN Decreases Expression [30]
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial (CYP27B1) OTTK98BH CP27B_HUMAN Decreases Expression [31]
Apoptosis-inducing factor 1, mitochondrial (AIFM1) OTKPWB7Q AIFM1_HUMAN Affects Localization [32]
Tropomyosin alpha-3 chain (TPM3) OT5RU5G6 TPM3_HUMAN Decreases Expression [33]
Growth-regulated alpha protein (CXCL1) OT3WCTZV GROA_HUMAN Affects Secretion [34]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [35]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Activity [36]
MHC class I polypeptide-related sequence A (MICA) OTPEIEAR MICA_HUMAN Decreases Expression [37]
Major histocompatibility complex class I-related gene protein (MR1) OTZU3XX7 HMR1_HUMAN Affects Expression [38]
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Increases Acetylation [39]
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⏷ Show the Full List of 13 DOT(s)

References

1 ClinicalTrials.gov (NCT03012763) Oral Pharmacokinetics of Sulfasalazine, Paracetamol, Fexofenadine and Valsartan Using Different Administration Mediums
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: 4819).
3 Fexofenadine FDA Label
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 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: 4840).
6 Sulfasalazine FDA Label
7 Update on prescription and over-the-counter histamine inverse agonists in rhinitis therapy. Curr Allergy Asthma Rep. 2009 Mar;9(2):140-8.
8 Effect of itraconazole on the pharmacokinetics and pharmacodynamics of fexofenadine in relation to the MDR1 genetic polymorphism. Clin Pharmacol Ther. 2005 Aug;78(2):191-201.
9 Intestinal drug transporter expression and the impact of grapefruit juice in humans. Clin Pharmacol Ther. 2007 Mar;81(3):362-70.
10 Involvement of multiple efflux transporters in hepatic disposition of fexofenadine. Mol Pharmacol. 2008 May;73(5):1474-83.
11 Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1. Biochem Pharmacol. 2010 Dec 1;80(11):1746-53.
12 Contribution of OATP (organic anion-transporting polypeptide) family transporters to the hepatic uptake of fexofenadine in humans. Drug Metab Dispos. 2005 Oct;33(10):1477-81.
13 The effects of the SLCO2B1 c.1457C>T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans. Pharmacogenet Genomics. 2011 Feb;21(2):84-93.
14 A variant 2677A allele of the MDR1 gene affects fexofenadine disposition. Clin Pharmacol Ther. 2004 Nov;76(5):418-27. doi: 10.1016/j.clpt.2004.08.002.
15 Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro. Int Arch Allergy Immunol. 2011;155(1):38-51. doi: 10.1159/000318720. Epub 2010 Nov 25.
16 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
17 Sulfasalazine down-regulates the expression of the angiogenic factors platelet-derived endothelial cell growth factor/thymidine phosphorylase and interleukin-8 in human monocytic-macrophage THP1 and U937 cells. Mol Pharmacol. 2004 Oct;66(4):1054-60.
18 [The effects of anti-inflammatory on activation of nuclear factor-kappaB and expression of cell adhesion molecules in patients with ulcerative colitis]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2004 Oct;21(5):732-6.
19 The anti-inflammatory mechanism of sulfasalazine is related to adenosine release at inflamed sites. J Immunol. 1996 Mar 1;156(5):1937-41.
20 Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96.
21 Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7.
22 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
23 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.
24 Small-Dosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1 and ABCG2), and Interaction (Atorvastatin and Grapefruit Juice) Profiles of 5 Probes for OATP2B1 and BCRP. J Pharm Sci. 2017 Sep;106(9):2688-2694.
25 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
26 The influence of probiotic treatment on sulfasalazine metabolism in rat. Xenobiotica. 2012 Aug;42(8):791-7.
27 The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J Pharmacol Exp Ther. 1972 Jun;181(3):555-62.
28 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
29 Chemotherapeutic drug-induced ABCG2 promoter demethylation as a novel mechanism of acquired multidrug resistance. Neoplasia. 2009 Dec;11(12):1359-70. doi: 10.1593/neo.91314.
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31 Down-regulation by nuclear factor kappaB of human 25-hydroxyvitamin D3 1alpha-hydroxylase promoter. Mol Endocrinol. 2004 Oct;18(10):2440-50. doi: 10.1210/me.2002-0441. Epub 2004 Jul 8.
32 Molecular mechanisms of sulfasalazine-induced T-cell apoptosis. Br J Pharmacol. 2002 Nov;137(5):608-20. doi: 10.1038/sj.bjp.0704870.
33 Mesalamine suppresses the expression of TC22, a novel tropomyosin isoform associated with colonic neoplasia. Mol Pharmacol. 2009 Jul;76(1):183-91. doi: 10.1124/mol.109.056028. Epub 2009 Apr 15.
34 The effect of sulfasalazine on rheumatoid arthritic synovial tissue chemokine production. Exp Mol Pathol. 2002 Oct;73(2):84-92. doi: 10.1006/exmp.2002.2460.
35 [Activation of nuclear factor-kappaB and its relationship with cytokine gene expression in colonic mucosa of ulcerative colitis patients]. Zhonghua Nei Ke Za Zhi. 2002 Apr;41(4):252-5.
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37 NF-kappa B regulates expression of the MHC class I-related chain A gene in activated T lymphocytes. J Immunol. 2004 Nov 1;173(9):5583-90. doi: 10.4049/jimmunol.173.9.5583.
38 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.
39 Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene. J Rheumatol. 2002 Dec;29(12):2492-9.