Details of the Drug Combination

General Information of Drug Combination (ID: DCGZFSP)

• Drug Combination Name: Mycophenolate mofetil + Mycophenolic acid
• Indication: Kidney Transplant; Status: Phase 1 [1]
• Component Drugs:
  Mycophenolate mofetil (DMPQAGE): Small molecular drug
  Mycophenolic acid (DMRBMAU): N.A.

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Mycophenolate mofetil

Disease Entry	ICD 11	Status	REF
Hepatosplenic T-cell lymphoma	N.A.	Approved	[2]
Interstitial cystitis	GC00.3	Approved	[2]
Large granular lymphocytic leukemia	2A90.1	Approved	[2]
Lupus nephritis	4A40.0Y	Approved	[2]
MALT lymphoma	N.A.	Approved	[2]
Myeloid leukaemia	2B33.1	Approved	[2]
Myeloproliferative neoplasm	2A20	Approved	[2]
Nodal marginal zone lymphoma	2A85.0	Approved	[2]
Organ transplant rejection	NE84	Approved	[3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[2]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[2]
Small intestine lymphoma	N.A.	Approved	[2]
Splenic marginal zone lymphoma	N.A.	Approved	[2]
Systemic lupus erythematosus	4A40.0	Approved	[2]
Testicular lymphoma	N.A.	Approved	[2]
Pemphigus vulgaris	EB40	Phase 3	[3]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Immune System disease	4A01-4B41	Investigative	[4]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[5]

Mycophenolate mofetil Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin E2 receptor EP2 (PTGER2)	TT1ZAVI	PE2R2_HUMAN	Modulator	[4]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	TTTB4UP	IMDH2_HUMAN	Inhibitor	[17]

Mycophenolate mofetil Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[18]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[19]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[19]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[18]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[18]

Mycophenolate mofetil Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[20]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[21]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[20]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[20]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[20]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[22]
UDP-glucuronosyltransferase 1A6 (UGT1A6)	DESD26P	UD16_HUMAN	Metabolism	[21]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[23]

Indication(s) of Mycophenolic acid

Disease Entry	ICD 11	Status	REF
Crohn disease	DD70	Approved	[6]
Hepatosplenic T-cell lymphoma	N.A.	Approved	[7]
Interstitial cystitis	GC00.3	Approved	[8]
Large granular lymphocytic leukemia	2A90.1	Approved	[7]
Leukemia	N.A.	Approved	[9]
Lupus nephritis	4A40.0Y	Approved	[10]
MALT lymphoma	N.A.	Approved	[7]
Myeloid leukaemia	2B33.1	Approved	[11]
Myeloproliferative neoplasm	2A20	Approved	[12]
Nodal marginal zone lymphoma	2A85.0	Approved	[7]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[7]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[7]
Small intestine lymphoma	N.A.	Approved	[7]
Splenic marginal zone lymphoma	N.A.	Approved	[7]
Systemic lupus erythematosus	4A40.0	Approved	[13]
Testicular lymphoma	N.A.	Approved	[7]
Classic Hodgkin lymphoma	N.A.	Investigative	[14]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[15]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[16]

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	[16]

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	[24]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[25]

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	[26]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[26]

References

• [1] ClinicalTrials.gov (NCT02711826) Treg Therapy in Subclinical Inflammation in Kidney Transplantation
• [2] Mycophenolate mofetil FDA Label
• [3] 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: 6831).
• [4] 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. (Target id: 341).
• [5] High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses. J Virol. 2019 May 29;93(12). pii: e00023-19.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
• [8] 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.
• [9] New conjugates of mycophenolic acid and their antiproliferative activity. J Asian Nat Prod Res. 2016 Nov;18(11):1057-62.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Systemic Lupus Erythematosus Management in Pregnancy. Int J Womens Health. 2022 Feb 15;14:199-211.
• [14] 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.
• [15] Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience. 2020 Mar 27;14:1022.
• [16] SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug;14(8):523-34.
• [17] Clinical pipeline report, company report or official report of Roche (2009).
• [18] Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
• [19] Influence of drug transporters and UGT polymorphisms on pharmacokinetics of phenolic glucuronide metabolite of mycophenolic acid in Japanese renal transplant recipients. Ther Drug Monit. 2008 Oct;30(5):559-64.
• [20] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [21] Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
• [22] The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011 Jan;50(1):1-24.
• [23] [Pharmacology of mycophenolate mofetil: recent data and clinical consequences]. Nephrologie. 2001;22(7):331-7.
• [24] 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.
• [25] 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.
• [26] 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.