Details of the Drug Combination

General Information of Drug Combination (ID: DCECNKR)

• Drug Combination Name: Cevimeline + Mycophenolic acid
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Cevimeline (DMWSMND): Small molecular drug
  Mycophenolic acid (DMRBMAU): N.A.
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 5.82
  Bliss Independence Score: 5.82
  Loewe Additivity Score: 7.5
  LHighest Single Agent (HSA) Score: 7.5

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cevimeline

Disease Entry	ICD 11	Status	REF
Sjogren syndrome	4A43.20	Approved	[2]

Cevimeline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Agonist	[14]

Cevimeline Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[15]

Indication(s) of Mycophenolic acid

Disease Entry	ICD 11	Status	REF
Crohn disease	DD70	Approved	[3]
Hepatosplenic T-cell lymphoma	N.A.	Approved	[4]
Interstitial cystitis	GC00.3	Approved	[5]
Large granular lymphocytic leukemia	2A90.1	Approved	[4]
Leukemia	N.A.	Approved	[6]
Lupus nephritis	4A40.0Y	Approved	[7]
MALT lymphoma	N.A.	Approved	[4]
Myeloid leukaemia	2B33.1	Approved	[8]
Myeloproliferative neoplasm	2A20	Approved	[9]
Nodal marginal zone lymphoma	2A85.0	Approved	[4]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[4]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[4]
Small intestine lymphoma	N.A.	Approved	[4]
Splenic marginal zone lymphoma	N.A.	Approved	[4]
Systemic lupus erythematosus	4A40.0	Approved	[10]
Testicular lymphoma	N.A.	Approved	[4]
Classic Hodgkin lymphoma	N.A.	Investigative	[11]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[12]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[13]

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	[13]

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	[16]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[17]

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	[18]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[18]

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] Therapeutic effect of cevimeline on dry eye in patients with Sj gren's syndrome: a randomized, double-blind clinical study. Am J Ophthalmol. 2004 Jul;138(1):6-17.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
• [5] 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.
• [6] New conjugates of mycophenolic acid and their antiproliferative activity. J Asian Nat Prod Res. 2016 Nov;18(11):1057-62.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Systemic Lupus Erythematosus Management in Pregnancy. Int J Womens Health. 2022 Feb 15;14:199-211.
• [11] 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.
• [12] Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience. 2020 Mar 27;14:1022.
• [13] SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug;14(8):523-34.
• [14] Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor ... Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G112-G123.
• [15] Pharmacokinetics and metabolism of the novel muscarinic receptor agonist SNI-2011 in rats and dogs. Arzneimittelforschung. 2003;53(1):26-33.
• [16] 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.
• [17] 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.
• [18] 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.