General Information of Drug Combination (ID: DCLJ519)

Drug Combination Name
Rolapitant Sulfasalazine
Indication
Disease Entry Status REF
Chemotherapy-induced Nausea and Vomiting Phase 1 [1]
Component Drugs Rolapitant   DM8XP26 Sulfasalazine   DMICA9H
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Rolapitant
Disease Entry ICD 11 Status REF
Chemotherapy-induced nausea MD90 Approved [2]
Rolapitant Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Substance-P receptor (TACR1) TTZPO1L NK1R_HUMAN Antagonist [6]
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Rolapitant Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
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Indication(s) of Sulfasalazine
Disease Entry ICD 11 Status REF
Irritable bowel syndrome DD91.0 Approved [3]
Rheumatoid arthritis FA20 Approved [4]
Ulcerative colitis DD71 Approved [5]
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 [10]
Nuclear factor NF-kappa-B (NFKB) TTSXVID NFKB1_HUMAN; NFKB2_HUMAN; TF65_HUMAN; RELB_HUMAN; REL_HUMAN Activator [11]
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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 [12]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [13]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [14]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [15]
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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 [16]
Azoreductase (azoR) DE5CAX1 A0A074IU04_STRSL Metabolism [17]
Azoreductase (azoR) DEGTKHL T0VG26_9ENTE Metabolism [18]
Azoreductase (azoR) DE3UF6Z A0A0P0ETC6_BACT4 Metabolism [18]
Azoreductase (azoR) DE6GHJ5 A0A0P0ETC6_BACT4 Metabolism [18]
Azoreductase (azoR) DEEISQ2 AZOR_ENTFA Metabolism [17]
Azoreductase (azoR) DEI2PC5 AZOR_CLOP1 Metabolism [17]
Azoreductase (azoR) DETEMAH A0A349MYB4_9LACO Metabolism [18]
Azoreductase (azoR) DEM1BHT A0A132Z973_ENTFC Metabolism [17]
Azoreductase (azoR) DEIKZOU A0A0P0ETC6_BACT4 Metabolism [19]
Azoreductase (azoR) DENLBG3 A0A0P0ETC6_BACT4 Metabolism [17]
Azoreductase (azoR) DEIHK8V A0A349MYB4_9LACO Metabolism [17]
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⏷ Show the Full List of 12 DME(s)
Sulfasalazine Interacts with 33 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 [20]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Decreases Expression [8]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Activity [21]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) OTQ4W7MT TR11B_HUMAN Increases Secretion [22]
Tumor necrosis factor ligand superfamily member 11 (TNFSF11) OTJEPKEQ TNF11_HUMAN Decreases Expression [22]
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) OT9RDS3H IKKB_HUMAN Decreases Expression [23]
Transmembrane protease serine 2 (TMPRSS2) OTN44YQ5 TMPS2_HUMAN Increases Expression [24]
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial (CYP27B1) OTTK98BH CP27B_HUMAN Decreases Expression [25]
Apoptosis-inducing factor 1, mitochondrial (AIFM1) OTKPWB7Q AIFM1_HUMAN Affects Localization [26]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Response To Substance [27]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [28]
Glucocorticoid receptor (NR3C1) OTCI2YDI GCR_HUMAN Increases Expression [29]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Decreases Expression [9]
Insulin receptor (INSR) OTTY341H INSR_HUMAN Increases Expression [23]
Tropomyosin alpha-3 chain (TPM3) OT5RU5G6 TPM3_HUMAN Decreases Expression [30]
Growth-regulated alpha protein (CXCL1) OT3WCTZV GROA_HUMAN Affects Secretion [31]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [28]
E-selectin (SELE) OT33RZWY LYAM2_HUMAN Increases Expression [32]
Thromboxane-A synthase (TBXAS1) OTAXZJJ4 THAS_HUMAN Decreases Activity [33]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Decreases Expression [34]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [26]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [35]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Activity [23]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Localization [26]
MHC class I polypeptide-related sequence A (MICA) OTPEIEAR MICA_HUMAN Decreases Expression [36]
Major histocompatibility complex class I-related gene protein (MR1) OTZU3XX7 HMR1_HUMAN Affects Expression [37]
Proton-coupled folate transporter (SLC46A1) OT049V7Y PCFT_HUMAN Decreases Activity [38]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Decreases Expression [24]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Decreases Activity [39]
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Increases Acetylation [40]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases ADR [41]
Myeloperoxidase (MPO) OTOOXLIN PERM_HUMAN Increases ADR [41]
Methylenetetrahydrofolate reductase (MTHFR) OTUBJSR7 MTHR_HUMAN Increases Response To Substance [42]
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⏷ Show the Full List of 33 DOT(s)

References

1 ClinicalTrials.gov (NCT02434861) An Open Label, Single Dose, Three Part Study to Assess the Effects of Rolapitant (2 mg/mL IV Solution) on the Pharmacokinetics of Digoxin; Sulfasalazine; and the Cooperstown Cocktail (Midazolam, Omeprazole, Warfarin, Caffeine, and Dextromethorphan in Healthy Subjects
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: 5749).
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 4840).
5 Sulfasalazine FDA Label
6 Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44.
7 Pharmacokinetic interactions of rolapitant with cytochrome P450 3A substrates in healthy subjects. J Clin Pharmacol. 2019 Apr;59(4):488-499.
8 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.
9 [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.
10 The anti-inflammatory mechanism of sulfasalazine is related to adenosine release at inflamed sites. J Immunol. 1996 Mar 1;156(5):1937-41.
11 Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96.
12 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.
13 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
14 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.
15 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.
16 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
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19 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
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21 Identification of chemical compounds that induce HIF-1alpha activity. Toxicol Sci. 2009 Nov;112(1):153-63.
22 Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor kappaB, osteoprotegerin, and receptor activator of nuclear factor kappaB ligand. Arthritis Rheum. 2004 Dec;50(12):3831-43. doi: 10.1002/art.20637.
23 Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro. Endocrinology. 2005 Mar;146(3):1491-7. doi: 10.1210/en.2004-0809. Epub 2004 Nov 24.
24 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
25 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.
26 Molecular mechanisms of sulfasalazine-induced T-cell apoptosis. Br J Pharmacol. 2002 Nov;137(5):608-20. doi: 10.1038/sj.bjp.0704870.
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29 Sulfasalazine sensitises human monocytic/macrophage cells for glucocorticoids by upregulation of glucocorticoid receptor alpha and glucocorticoid induced apoptosis. Ann Rheum Dis. 2007 Oct;66(10):1289-95. doi: 10.1136/ard.2006.060509. Epub 2007 Jan 31.
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34 Nuclear factor-kappa B activation in human testicular apoptosis. Am J Pathol. 2002 Jan;160(1):205-18. doi: 10.1016/s0002-9440(10)64364-7.
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36 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.
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38 Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther. 2007 Aug;322(2):469-76. doi: 10.1124/jpet.107.122606. Epub 2007 May 2.
39 Pharmacogenomic approach reveals a role for the x(c)- cystine/glutamate antiporter in growth and celastrol resistance of glioma cell lines. J Pharmacol Exp Ther. 2010 Mar;332(3):949-58. doi: 10.1124/jpet.109.162248. Epub 2009 Dec 9.
40 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.
41 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.
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