General Information of Drug Combination (ID: DCWW075)

Drug Combination Name
Mycophenolic acid Allopurinol
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Mycophenolic acid   DMRBMAU Allopurinol   DMLPAOB
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 1.22
Bliss Independence Score: 1.22
Loewe Additivity Score: 1.94
LHighest Single Agent (HSA) Score: 1.98

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 Allopurinol
Disease Entry ICD 11 Status REF
Gout FA25 Approved [13]
Hyperuricaemia 5C55.Y Approved [14]
Recurrent adult burkitt lymphoma 2A85.6 Approved [13]
Allopurinol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Xanthine dehydrogenase/oxidase (XDH) TT7RJY8 XDH_HUMAN Inhibitor [19]
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Allopurinol Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporter 2 (SLC22A7) DT0OC1Q S22A7_HUMAN Substrate [20]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [21]
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Allopurinol Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
RNA cytidine acetyltransferase (hALP) DEZV4AP NAT10_HUMAN Metabolism [22]
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Allopurinol Interacts with 30 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier family 22 member 7 (SLC22A7) OTKTNH1W S22A7_HUMAN Increases Transport [23]
HLA class I histocompatibility antigen, B alpha chain (HLA-B) OTNXFWY2 HLAB_HUMAN Increases Response To Substance [24]
HLA class I histocompatibility antigen, C alpha chain (HLA-C) OTV38BUJ HLAC_HUMAN Increases ADR [25]
HLA class I histocompatibility antigen, A alpha chain (HLA-A) OTAH14LU HLAA_HUMAN Increases ADR [26]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1) OTVVI3UI DQB1_HUMAN Increases ADR [25]
Transmembrane protease serine 2 (TMPRSS2) OTN44YQ5 TMPS2_HUMAN Decreases Expression [27]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [28]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [29]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [30]
Apolipoprotein C-III (APOC3) OTW3520C APOC3_HUMAN Decreases Expression [28]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Decreases Expression [28]
Protein disulfide-isomerase (P4HB) OTTYNYPF PDIA1_HUMAN Decreases Expression [28]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [31]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [31]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [28]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [30]
Platelet glycoprotein 4 (CD36) OT5CZWKY CD36_HUMAN Decreases Expression [28]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6) OTAFHAVI ATF6A_HUMAN Increases Expression [28]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [30]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [30]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [28]
Microsomal triglyceride transfer protein large subunit (MTTP) OTNUVSDT MTP_HUMAN Decreases Expression [28]
Cytochrome P450 4A11 (CYP4A11) OTPU5J0S CP4AB_HUMAN Increases Expression [32]
Peroxisome proliferator-activated receptor alpha (PPARA) OTK095PP PPARA_HUMAN Increases Expression [32]
Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) OTM0A0DY ACOX1_HUMAN Increases Expression [32]
Angiopoietin-related protein 3 (ANGPTL3) OTCD5Z9W ANGL3_HUMAN Decreases Expression [28]
Glycophorin-A (GYPA) OTABU4YV GLPA_HUMAN Increases ADR [33]
Myeloperoxidase (MPO) OTOOXLIN PERM_HUMAN Increases ADR [33]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Increases ADR [33]
HLA class I histocompatibility antigen protein P5 (HCP5) OTV0YRI8 HCP5_HUMAN Increases ADR [34]
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⏷ Show the Full List of 30 DOT(s)

References

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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.
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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.
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11 Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience. 2020 Mar 27;14:1022.
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13 Allopurinol FDA Label
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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 Uric acid-lowering treatment with benzbromarone in patients with heart failure: a double-blind placebo-controlled crossover preliminary study. Circ Heart Fail. 2010 Jan;3(1):73-81.
19 Allopurinol: xanthine oxidase inhibitor. Tex Med. 1966 Jan;62(1):100-1.
20 Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol. 2002 Jul;62(1):7-14.
21 Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83.
22 Xanthine oxidase inhibition by allopurinol affects the reliability of urinary caffeine metabolic ratios as markers for N-acetyltransferase 2 and CYP1A2 activities. Eur J Clin Pharmacol. 1999 Jan;54(11):869-76.
23 Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8.
24 HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4134-9. doi: 10.1073/pnas.0409500102. Epub 2005 Mar 2.
25 A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis. Int J Immunogenet. 2011 Aug;38(4):303-9. doi: 10.1111/j.1744-313X.2011.01011.x. Epub 2011 May 4.
26 Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics. 2011 May;21(5):303-7. doi: 10.1097/FPC.0b013e32834282b8.
27 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.
28 Drug-induced hepatic steatosis in absence of severe mitochondrial dysfunction in HepaRG cells: proof of multiple mechanism-based toxicity. Cell Biol Toxicol. 2021 Apr;37(2):151-175. doi: 10.1007/s10565-020-09537-1. Epub 2020 Jun 14.
29 Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. Toxicol Sci. 2003 Aug;74(2):260-70. doi: 10.1093/toxsci/kfg113. Epub 2003 May 2.
30 Allopurinol induces innate immune responses through mitogen-activated protein kinase signaling pathways in HL-60 cells. J Appl Toxicol. 2016 Sep;36(9):1120-8. doi: 10.1002/jat.3272. Epub 2015 Dec 7.
31 Systemic drugs inducing non-immediate cutaneous adverse reactions and contact sensitizers evoke similar responses in THP-1 cells. J Appl Toxicol. 2015 Apr;35(4):398-406. doi: 10.1002/jat.3033. Epub 2014 Aug 4.
32 Allopurinol Protects Against Cholestatic Liver Injury in Mice Not Through Depletion of Uric Acid. Toxicol Sci. 2021 May 27;181(2):295-305. doi: 10.1093/toxsci/kfab034.
33 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.
34 Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013 Feb;93(2):153-8. doi: 10.1038/clpt.2012.209. Epub 2012 Oct 17.