Details of the Drug Combination

General Information of Drug Combination (ID: DCWJNC3)

Drug Combination Name
Everolimus Tacrolimus
Indication
Disease Entry Status REF
Delayed Graft Function Phase 2 [1]
Component Drugs Everolimus   DM8X2EH Tacrolimus   DMZ7XNQ
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 Everolimus
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [2]
Advanced/metastatic breast cancer 2C60 Approved [3]
Brainstem neoplasm N.A. Approved [2]
Breast carcinoma N.A. Approved [2]
Graft-versus-host disease 4B24 Approved [2]
Intracranial meningioma N.A. Approved [2]
Leukemia N.A. Approved [2]
Lung cancer 2C25.0 Approved [2]
Mucosal melanoma N.A. Approved [2]
Multiple sclerosis 8A40 Approved [2]
Plasma cell myeloma 2A83.1 Approved [2]
Prostate cancer 2C82.0 Approved [2]
Renal cell carcinoma 2C90 Approved [4]
Salivary gland squamous cell carcinoma N.A. Approved [2]
Tuberous sclerosis LD2D.2 Approved [2]
Kidney cancer 2C90.0 Phase 3 [4]
Castration-resistant prostate carcinoma N.A. Investigative [2]
Colon cancer 2B90.Z Investigative [2]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [5]
Neuroblastoma 2D11.2 Investigative [2]
Pancreatic acinar cell carcinoma N.A. Investigative [2]
Polycystic kidney disease GB8Y Investigative [2]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [5]
Everolimus Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [8]
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [5]
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Everolimus Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
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Everolimus Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
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Indication(s) of Tacrolimus
Disease Entry ICD 11 Status REF
Graft-versus-host disease 4B24 Approved [6]
Hepatosplenic T-cell lymphoma N.A. Approved [6]
Kidney transplant rejection NE84 Approved [6]
Large granular lymphocytic leukemia 2A90.1 Approved [6]
Leukemia N.A. Approved [6]
Lupus nephritis 4A40.0Y Approved [6]
MALT lymphoma N.A. Approved [6]
Myeloproliferative neoplasm 2A20 Approved [6]
Nodal marginal zone lymphoma 2A85.0 Approved [6]
Organ transplant rejection NE84 Approved [7]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [6]
Recurrent adult burkitt lymphoma 2A85.6 Approved [6]
Small intestine lymphoma N.A. Approved [6]
Splenic marginal zone lymphoma N.A. Approved [6]
Testicular lymphoma N.A. Approved [6]
Ocular allergy 4A81 Phase 3 [7]
Classic Hodgkin lymphoma N.A. Investigative [6]
Tacrolimus Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Calcineurin (PPP3CA) TTA4LDE PP2BA_HUMAN Inhibitor [13]
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Tacrolimus Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [14]
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Tacrolimus Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [15]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [16]
NADPH-cytochrome P450 reductase (CPR) DE3N2FM NCPR_HUMAN Metabolism [17]
Ribosomal 23S RNA methyltransferase Erm (erm) DEW6V07 A0A5N1AHF6_CORAY Metabolism [18]
Ribosomal 23S RNA methyltransferase Erm (erm) DEA65D8 A0A381KDL2_CORJE Metabolism [18]
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Tacrolimus Interacts with 49 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Methylation [19]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Decreases Methylation [19]
NADPH--cytochrome P450 reductase (POR) OTVIDOCH NCPR_HUMAN Affects Response To Substance [20]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Response To Substance [21]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [22]
Cytochrome b-245 light chain (CYBA) OT16N9ZO CY24A_HUMAN Increases Expression [22]
Nitric oxide synthase 3 (NOS3) OTLDT7NR NOS3_HUMAN Increases Expression [22]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [23]
Natural cytotoxicity triggering receptor 3 (NCR3) OT20M764 NCTR3_HUMAN Increases Expression [24]
Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) OTCYYCAC HGS_HUMAN Increases Expression [12]
Rho guanine nucleotide exchange factor 11 (ARHGEF11) OTDOMEH6 ARHGB_HUMAN Increases Expression [12]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [25]
Actin-related protein 2/3 complex subunit 5 (ARPC5) OTFNMMDL ARPC5_HUMAN Increases Expression [12]
G2/mitotic-specific cyclin-B2 (CCNB2) OTIEXTDK CCNB2_HUMAN Decreases Expression [25]
Zinc finger protein SNAI1 (SNAI1) OTDPYAMC SNAI1_HUMAN Increases Expression [11]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Expression [26]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [27]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Decreases Expression [28]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [29]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Increases Expression [30]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Increases Expression [30]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Decreases Expression [28]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [28]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Expression [31]
Interleukin-3 (IL3) OT0CQ35N IL3_HUMAN Decreases Expression [28]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [32]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Decreases Expression [11]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Expression [31]
Ras-related protein Rab-4A (RAB4A) OT7BL9WW RAB4A_HUMAN Increases Expression [12]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Decreases Degradation [27]
T-lymphocyte activation antigen CD80 (CD80) OTJBLUQE CD80_HUMAN Decreases Expression [33]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [33]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [34]
Troponin T, cardiac muscle (TNNT2) OT80NN7R TNNT2_HUMAN Increases Expression [35]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Decreases Secretion [36]
Glycogen synthase kinase-3 alpha (GSK3A) OT0F6DWV GSK3A_HUMAN Increases Phosphorylation [11]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [11]
Eotaxin (CCL11) OT3BIFPK CCL11_HUMAN Decreases Expression [31]
C-C chemokine receptor type 3 (CCR3) OT6GBUFA CCR3_HUMAN Decreases Expression [31]
LIM domain kinase 1 (LIMK1) OTFZ8MZ0 LIMK1_HUMAN Increases Expression [12]
Interleukin-2 (IL2) OTGI4NSA IL2_HUMAN Decreases Expression [28]
Neutrophil gelatinase-associated lipocalin (LCN2) OTSB42BR NGAL_HUMAN Increases Expression [30]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [34]
Lethal(2) giant larvae protein homolog 1 (LLGL1) OTAIQSXZ L2GL1_HUMAN Increases Expression [12]
Calcineurin subunit B type 1 (PPP3R1) OTGQNFJQ CANB1_HUMAN Increases ADR [37]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Response To Substance [38]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Response To Substance [38]
Peroxisome proliferator-activated receptor alpha (PPARA) OTK095PP PPARA_HUMAN Affects Response To Substance [20]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Decreases Methylation [19]
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⏷ Show the Full List of 49 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Liver Transplantation DC8BWRX N. A. Phase 3 [39]
Chronic myelogenous leukemia DCTB9F9 KBM-7 Investigative [40]
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References

1 ClinicalTrials.gov (NCT01878786) A Pilot Study Comparing the Safety and Efficacy of Everolimus With Other Medicines in Recipients of ECD/DCD Kidneys
2 Everolimus FDA Label
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: 5889).
5 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
6 Tacrolimus FDA Label
7 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: 6784).
8 Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
9 Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations. Ther Drug Monit. 2015 Oct;37(5):675-80.
10 The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.
11 GSK3, snail, and adhesion molecule regulation by cyclosporine A in renal tubular cells. Toxicol Sci. 2012 Jun;127(2):425-37. doi: 10.1093/toxsci/kfs108. Epub 2012 Mar 12.
12 Calcineurin is an important factor involved in glucose uptake in human adipocytes. Mol Cell Biochem. 2018 Aug;445(1-2):157-168. doi: 10.1007/s11010-017-3261-0. Epub 2018 Jan 27.
13 Emerging drugs for ocular allergy. Expert Opin Emerg Drugs. 2005 Aug;10(3):505-20.
14 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
15 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
16 Tacrolimus pharmacokinetics and pharmacogenetics: influence of adenosine triphosphate-binding cassette B1 (ABCB1) and cytochrome (CYP) 3A polymorphisms. Fundam Clin Pharmacol. 2007 Aug;21(4):427-35.
17 Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy. Pharmacogenet Genomics. 2017 Sep;27(9):337-346.
18 High frequency of macrolide resistance mechanisms in clinical isolates of Corynebacterium species. Microb Drug Resist. 2010 Dec;16(4):273-7.
19 Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus. Clin Chem. 2005 Aug;51(8):1374-81.
20 Single-nucleotide polymorphisms in P450 oxidoreductase and peroxisome proliferator-activated receptor- are associated with the development of new-onset diabetes after transplantation in kidney transplant recipients treated with tacrolimus. Pharmacogenet Genomics. 2013 Dec;23(12):649-57. doi: 10.1097/FPC.0000000000000001.
21 Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene. Transplantation. 2002 Aug 27;74(4):571-2. doi: 10.1097/00007890-200208270-00024.
22 Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril. J Cardiovasc Pharmacol. 2002 Oct;40(4):625-31.
23 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
24 Mycophenolic acid inhibits natural killer cell proliferation and cytotoxic function: a possible disadvantage of including mycophenolate mofetil in the graft-versus-host disease prophylaxis regimen. Biol Blood Marrow Transplant. 2011 Feb;17(2):205-13. doi: 10.1016/j.bbmt.2010.08.014. Epub 2010 Aug 22.
25 CyclinB2 and BIRC5 genes as surrogate biomarkers for neurite outgrowth in SH-SY5Y subclonal cells. Neuropharmacology. 2006 Jun;50(8):1041-7. doi: 10.1016/j.neuropharm.2006.02.004. Epub 2006 Mar 30.
26 Effects of immunosuppressive drugs on in vitro neogenesis of human islets: mycophenolate mofetil inhibits the proliferation of ductal cells. Am J Transplant. 2007 Apr;7(4):1021-6. doi: 10.1111/j.1600-6143.2006.01728.x.
27 FK506 inhibits tumour necrosis factor-alpha secretion in human keratinocytes via regulation of nuclear factor-kappaB. Br J Dermatol. 2005 Oct;153(4):725-32. doi: 10.1111/j.1365-2133.2005.06779.x.
28 Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids). Int Immunopharmacol. 2001 Jun;1(6):1219-26. doi: 10.1016/s1567-5769(01)00059-5.
29 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.
30 Tacrolimus-induced nephrotoxicity in mice is associated with microRNA deregulation. Arch Toxicol. 2018 Apr;92(4):1539-1550. doi: 10.1007/s00204-018-2158-3. Epub 2018 Jan 23.
31 Tacrolimus decreases the expression of eotaxin, CCR3, RANTES and interleukin-5 in atopic dermatitis. Br J Dermatol. 2005 Jun;152(6):1173-81. doi: 10.1111/j.1365-2133.2005.06474.x.
32 A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
33 Tacrolimus ointment causes inflammatory dendritic epidermal cell depletion but no Langerhans cell apoptosis in patients with atopic dermatitis. J Allergy Clin Immunol. 2004 Jul;114(1):137-43. doi: 10.1016/j.jaci.2004.03.021.
34 Immunosuppressive calcineurin inhibitor cyclosporine A?induces proapoptotic endoplasmic reticulum stress in renal tubular cells. J Biol Chem. 2022 Mar;298(3):101589. doi: 10.1016/j.jbc.2022.101589. Epub 2022 Jan 14.
35 Multicenter prospective investigation on cardiovascular adverse effects of tacrolimus in kidney transplantations. Cardiovasc Drugs Ther. 2003 Mar;17(2):141-9. doi: 10.1023/a:1025339819051.
36 Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis. J Allergy Clin Immunol. 2001 Nov;108(5):839-46. doi: 10.1067/mai.2001.118796.
37 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.
38 Hydrogen peroxide mediates FK506-induced cytotoxicity in renal cells. Kidney Int. 2004 Jan;65(1):139-47. doi: 10.1111/j.1523-1755.2004.00380.x.
39 ClinicalTrials.gov (NCT02115113) REnal Function in Liver Transplantation: Everolimus With Calcineurin Inhibitor (CNI)-Sparing sTrategy
40 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.