Details of the Drug Combination

General Information of Drug Combination (ID: DCI70YI)

• Drug Combination Name: Mycophenolic acid + Dantrolene
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Mycophenolic acid (DMRBMAU): N.A.
  Dantrolene (DM1D8XY): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 3.58
  Bliss Independence Score: 3.58
  Loewe Additivity Score: 6.21
  LHighest Single Agent (HSA) Score: 6.24

Molecular Interaction Atlas of This Drug Combination

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 Dantrolene

Disease Entry	ICD 11	Status	REF
Hyperthermia	MG26	Approved	[13]

Dantrolene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Ryanodine receptor (RYR)	TT9YXM1	NOUNIPROTAC	Modulator	[17]

Dantrolene Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[18]

Dantrolene Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Insulin-like growth factor II (IGF2)	OTJ4O6MW	IGF2_HUMAN	Decreases Response To Substance	[19]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Decreases Response To Substance	[19]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[20]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Increases Expression	[21]

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.
• [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: 4172).
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [18] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [19] Insulin-like growth factors (IGF) I and II utilize different calcium signaling pathways in a primary human parathyroid cell culture model. World J Surg. 2006 Mar;30(3):333-45. doi: 10.1007/s00268-005-0339-8.
• [20] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
• [21] 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.