General Information of Drug Combination (ID: DC54ACO)

Drug Combination Name
Mycophenolic acid Chlorzoxazone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Mycophenolic acid   DMRBMAU Chlorzoxazone   DMCYVDT
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: 0.62
Bliss Independence Score: 0.62
Loewe Additivity Score: 4.52
LHighest Single Agent (HSA) Score: 4.55

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]
------------------------------------------------------------------------------------
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 [14]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [15]
------------------------------------------------------------------------------------
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 [16]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [16]
------------------------------------------------------------------------------------
Indication(s) of Chlorzoxazone
Disease Entry ICD 11 Status REF
Acute pain MG31 Approved [13]
Chlorzoxazone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Calcium-activated potassium channel (KCN) TTMNI76 NOUNIPROTAC Activator [18]
------------------------------------------------------------------------------------
Chlorzoxazone Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [19]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [20]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [21]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [21]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [22]
Cytochrome P450 102A1 (cyp102) DE4OGUF CPXB_BACMB Metabolism [23]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DME(s)
Chlorzoxazone Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Intermediate conductance calcium-activated potassium channel protein 4 (KCNN4) OTQKQ346 KCNN4_HUMAN Increases Activity [24]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [25]
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Affects Metabolism [17]
------------------------------------------------------------------------------------

References

1 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.
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 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: 2322).
14 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.
15 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.
16 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.
17 Effects of cigarette smoking and carbon monoxide on chlorzoxazone and caffeine metabolism. Clin Pharmacol Ther. 2003 Nov;74(5):468-74. doi: 10.1016/j.clpt.2003.07.001.
18 Chlorzoxazone inhibits contraction of rat thoracic aorta. Eur J Pharmacol. 2006 Sep 18;545(2-3):161-6.
19 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
20 Inhibitory monoclonal antibodies to human cytochrome P450 1A2: analysis of phenacetin O-deethylation in human liver. Pharmacogenetics. 1998 Oct;8(5):375-82.
21 Prediction of human liver microsomal oxidations of 7-ethoxycoumarin and chlorzoxazone with kinetic parameters of recombinant cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Nov;27(11):1274-80.
22 Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7.
23 Wild-type CYP102A1 as a biocatalyst: turnover of drugs usually metabolised by human liver enzymes. J Biol Inorg Chem. 2007 Mar;12(3):313-23.
24 Functional and molecular identification of intermediate-conductance Ca(2+)-activated K(+) channels in breast cancer cells: association with cell cycle progression. Am J Physiol Cell Physiol. 2004 Jul;287(1):C125-34. doi: 10.1152/ajpcell.00488.2003. Epub 2004 Feb 25.
25 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.