Details of the Drug Combination

General Information of Drug Combination (ID: DC4MCMW)

Drug Combination Name
Mycophenolic acid Tacrolimus
Indication
Disease Entry Status REF
Immunosuppression After Renal Transplantation Phase 4 [1]
Component Drugs Mycophenolic acid   DMRBMAU Tacrolimus   DMZ7XNQ
N.A. 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 Mycophenolic acid
Disease Entry ICD 11 Status REF
Crohn disease DD70 Approved [2]
Hepatosplenic T-cell lymphoma N.A. Approved [3]
Interstitial cystitis GC00.3 Approved [4]
Large granular lymphocytic leukemia 2A90.1 Approved [3]
Leukemia N.A. Approved [5]
Lupus nephritis 4A40.0Y Approved [6]
MALT lymphoma N.A. Approved [3]
Myeloid leukaemia 2B33.1 Approved [7]
Myeloproliferative neoplasm 2A20 Approved [8]
Nodal marginal zone lymphoma 2A85.0 Approved [3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [3]
Recurrent adult burkitt lymphoma 2A85.6 Approved [3]
Small intestine lymphoma N.A. Approved [3]
Splenic marginal zone lymphoma N.A. Approved [3]
Systemic lupus erythematosus 4A40.0 Approved [9]
Testicular lymphoma N.A. Approved [3]
Classic Hodgkin lymphoma N.A. Investigative [10]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [11]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [12]
Mycophenolic acid Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MERS-CoV papain-like proteinase (PL-PRO) TTYJOLE R1AB_CVEMC (854-2740) Inhibitor [12]
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Mycophenolic acid Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [15]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [16]
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Mycophenolic acid Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [17]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [17]
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Indication(s) of Tacrolimus
Disease Entry ICD 11 Status REF
Graft-versus-host disease 4B24 Approved [13]
Hepatosplenic T-cell lymphoma N.A. Approved [13]
Kidney transplant rejection NE84 Approved [13]
Large granular lymphocytic leukemia 2A90.1 Approved [13]
Leukemia N.A. Approved [13]
Lupus nephritis 4A40.0Y Approved [13]
MALT lymphoma N.A. Approved [13]
Myeloproliferative neoplasm 2A20 Approved [13]
Nodal marginal zone lymphoma 2A85.0 Approved [13]
Organ transplant rejection NE84 Approved [14]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [13]
Recurrent adult burkitt lymphoma 2A85.6 Approved [13]
Small intestine lymphoma N.A. Approved [13]
Splenic marginal zone lymphoma N.A. Approved [13]
Testicular lymphoma N.A. Approved [13]
Ocular allergy 4A81 Phase 3 [14]
Classic Hodgkin lymphoma N.A. Investigative [13]
Tacrolimus Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Calcineurin (PPP3CA) TTA4LDE PP2BA_HUMAN Inhibitor [20]
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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 [21]
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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 [22]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [23]
NADPH-cytochrome P450 reductase (CPR) DE3N2FM NCPR_HUMAN Metabolism [24]
Ribosomal 23S RNA methyltransferase Erm (erm) DEW6V07 A0A5N1AHF6_CORAY Metabolism [25]
Ribosomal 23S RNA methyltransferase Erm (erm) DEA65D8 A0A381KDL2_CORJE Metabolism [25]
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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 [26]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Decreases Methylation [26]
NADPH--cytochrome P450 reductase (POR) OTVIDOCH NCPR_HUMAN Affects Response To Substance [27]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Response To Substance [28]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [29]
Cytochrome b-245 light chain (CYBA) OT16N9ZO CY24A_HUMAN Increases Expression [29]
Nitric oxide synthase 3 (NOS3) OTLDT7NR NOS3_HUMAN Increases Expression [29]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [30]
Natural cytotoxicity triggering receptor 3 (NCR3) OT20M764 NCTR3_HUMAN Increases Expression [31]
Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) OTCYYCAC HGS_HUMAN Increases Expression [19]
Rho guanine nucleotide exchange factor 11 (ARHGEF11) OTDOMEH6 ARHGB_HUMAN Increases Expression [19]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [32]
Actin-related protein 2/3 complex subunit 5 (ARPC5) OTFNMMDL ARPC5_HUMAN Increases Expression [19]
G2/mitotic-specific cyclin-B2 (CCNB2) OTIEXTDK CCNB2_HUMAN Decreases Expression [32]
Zinc finger protein SNAI1 (SNAI1) OTDPYAMC SNAI1_HUMAN Increases Expression [18]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Expression [33]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [34]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Decreases Expression [35]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [36]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Increases Expression [37]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Increases Expression [37]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Decreases Expression [35]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [35]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Expression [38]
Interleukin-3 (IL3) OT0CQ35N IL3_HUMAN Decreases Expression [35]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [39]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Decreases Expression [18]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Expression [38]
Ras-related protein Rab-4A (RAB4A) OT7BL9WW RAB4A_HUMAN Increases Expression [19]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Decreases Degradation [34]
T-lymphocyte activation antigen CD80 (CD80) OTJBLUQE CD80_HUMAN Decreases Expression [40]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [40]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [41]
Troponin T, cardiac muscle (TNNT2) OT80NN7R TNNT2_HUMAN Increases Expression [42]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Decreases Secretion [43]
Glycogen synthase kinase-3 alpha (GSK3A) OT0F6DWV GSK3A_HUMAN Increases Phosphorylation [18]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [18]
Eotaxin (CCL11) OT3BIFPK CCL11_HUMAN Decreases Expression [38]
C-C chemokine receptor type 3 (CCR3) OT6GBUFA CCR3_HUMAN Decreases Expression [38]
LIM domain kinase 1 (LIMK1) OTFZ8MZ0 LIMK1_HUMAN Increases Expression [19]
Interleukin-2 (IL2) OTGI4NSA IL2_HUMAN Decreases Expression [35]
Neutrophil gelatinase-associated lipocalin (LCN2) OTSB42BR NGAL_HUMAN Increases Expression [37]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [41]
Lethal(2) giant larvae protein homolog 1 (LLGL1) OTAIQSXZ L2GL1_HUMAN Increases Expression [19]
Calcineurin subunit B type 1 (PPP3R1) OTGQNFJQ CANB1_HUMAN Increases ADR [44]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Response To Substance [45]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Response To Substance [45]
Peroxisome proliferator-activated receptor alpha (PPARA) OTK095PP PPARA_HUMAN Affects Response To Substance [27]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Decreases Methylation [26]
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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 DCO9SR3 N. A. Phase 4 [46]
Liver Transplantation DC33EJM N. A. Phase 1 [47]
Chronic Allograft Injury DCINLK5 N. A. Phase 1 [48]
Chronic myelogenous leukemia DCE81TA KBM-7 Investigative [49]
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References

1 ClinicalTrials.gov (NCT02453867) Efficacy and Safety of a Reduced Immunosuppression vs. Standard Triple Therapy in Senior Renal Transplant Recipients
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
4 Early termination of a trial of mycophenolate mofetil for treatment of interstitial cystitis/painful bladder syndrome: lessons learned. J Urol. 2011 Mar;185(3):901-6.
5 New conjugates of mycophenolic acid and their antiproliferative activity. J Asian Nat Prod Res. 2016 Nov;18(11):1057-62.
6 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020 Jun;79(6):713-723.
7 Mycophenolic Acid overcomes imatinib and nilotinib resistance of chronic myeloid leukemia cells by apoptosis or a senescent-like cell cycle arrest. Leuk Res Treatment. 2012;2012:861301.
8 Thiotepa, Busulfan, and Fludarabine Conditioning Regimen in T Cell-Replete HLA-Haploidentical Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2019 Jul;25(7):1407-1415.
9 Systemic Lupus Erythematosus Management in Pregnancy. Int J Womens Health. 2022 Feb 15;14:199-211.
10 Identification of potential drugs for diffuse large b-cell lymphoma based on bioinformatics and Connectivity Map database. Pathol Res Pract. 2018 Nov;214(11):1854-1867.
11 Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience. 2020 Mar 27;14:1022.
12 SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug;14(8):523-34.
13 Tacrolimus FDA Label
14 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).
15 C-440T/T-331C polymorphisms in the UGT1A9 gene affect the pharmacokinetics of mycophenolic acid in kidney transplantation. Pharmacogenomics. 2007 Sep;8(9):1127-41.
16 Interaction and transport characteristics of mycophenolic acid and its glucuronide via human organic anion transporters hOAT1 and hOAT3. Biochem Pharmacol. 2007 Jun 30;74(1):161-8.
17 Diabetes mellitus reduces activity of human UDP-glucuronosyltransferase 2B7 in liver and kidney leading to decreased formation of mycophenolic acid acyl-glucuronide metabolite. Drug Metab Dispos. 2011 Mar;39(3):448-55.
18 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.
19 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.
20 Emerging drugs for ocular allergy. Expert Opin Emerg Drugs. 2005 Aug;10(3):505-20.
21 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.
22 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
23 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.
24 Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy. Pharmacogenet Genomics. 2017 Sep;27(9):337-346.
25 High frequency of macrolide resistance mechanisms in clinical isolates of Corynebacterium species. Microb Drug Resist. 2010 Dec;16(4):273-7.
26 Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus. Clin Chem. 2005 Aug;51(8):1374-81.
27 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.
28 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.
29 Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril. J Cardiovasc Pharmacol. 2002 Oct;40(4):625-31.
30 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
31 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.
32 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.
33 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.
34 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.
35 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.
36 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.
37 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.
38 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.
39 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.
40 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.
41 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.
42 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.
43 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.
44 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.
45 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.
46 ClinicalTrials.gov (NCT02123108) Safety and Efficacy of Basiliximab, Delayed Dose Tacrolimus Plus ECMPA (Enteric Coated Mycophenolic Acid) Following Liver Transplantation
47 ClinicalTrials.gov (NCT01018914) A Study to Compare Safety and Efficacy of Prograf + Myfortic and Advagraf + Myfortic in Liver Transplantation Patients
48 ClinicalTrials.gov (NCT01473732) Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity
49 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.