Details of the Drug Combination

General Information of Drug Combination (ID: DCMN5XC)

• Drug Combination Name: Mycophenolate mofetil + Cyclosporin A
• Indication: Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; Status: Phase 1 [1]
• Component Drugs:
  Mycophenolate mofetil (DMPQAGE): Small molecular drug
  Cyclosporin A (DMUYKBZ): Small molecular drug

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	[16]

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	[17]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[18]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[18]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[17]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[17]

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	[19]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[20]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[19]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[19]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[19]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[21]
UDP-glucuronosyltransferase 1A6 (UGT1A6)	DESD26P	UD16_HUMAN	Metabolism	[20]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[22]

Indication(s) of Cyclosporin A

Disease Entry	ICD 11	Status	REF
Adult acute monocytic leukemia	N.A.	Approved	[6]
Bronchiolitis obliterans syndrome	N.A.	Approved	[7]
Large granular lymphocytic leukemia	2A90.1	Approved	[8]
Leukemia	N.A.	Approved	[9]
Lupus nephritis	4A40.0Y	Approved	[10]
Myeloid leukaemia	2B33.1	Approved	[11]
Psoriasis	EA90	Approved	[12]
Xerophthalmia	5B55.Y	Approved	[13]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 1	[14]
Corneal disease	9A78.Z	Investigative	[15]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Kidney Transplantation	DC66M1D	N. A.	Phase 4	[23]
Liver Transplantation	DCNKNWM	N. A.	Phase 4	[24]
Dyskeratosis Congenita	DCZHK3W	N. A.	Phase 2	[25]
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities	DCXMKNG	N. A.	Phase 2	[26]
Accelerated Phase Chronic Myelogenous Leukemia	DC6CQ1B	N. A.	Phase 1	[27]
Kidney Dysfunction	DC6PKR5	N. A.	Phase 1	[28]
Adenosine Deaminase Deficiency	DCUQUC3	N. A.	Phase 1	[29]
Adult Acute Myeloid Leukemia in Remission	DC1564L	N. A.	Phase 1	[30]
Recurrent Renal Cell Cancer	DCUTAIB	N. A.	Phase 1	[31]

References

• [1] ClinicalTrials.gov (NCT00014235) Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies
• [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] Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia. Haematologica. 2023 Jan 1;108(1):61-68.
• [7] Bronchiolitis obliterans syndrome is associated with increased senescent lymphocytes in the small airways. J Heart Lung Transplant. 2021 Feb;40(2):108-119.
• [8] Rituximab for rheumatoid arthritis-associated large granular lymphocytic leukemia, a retrospective case series. Semin Arthritis Rheum. 2020 Oct;50(5):1109-1113.
• [9] Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways. Reprod Biol Endocrinol. 2020 Oct 12;18(1):100.
• [10] Efficacy and safety of Iguratimod as an add-on therapy for refractory lupus nephritis: A preliminary investigational study. Front Immunol. 2023 Mar 8;14:1062919.
• [11] Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2024 Feb;11(2):e127-e135.
• [12] Pustular psoriasis. Cutis. 1993 Jan;51(1):29-32.
• [13] Cyclosporin A (CyA) in primary Sj?gren's syndrome: a double blind study. Ann Rheum Dis. 1986 Sep;45(9):732-5.
• [14] Why Choose Cyclosporin A as First-line Therapy in COVID-19 Pneumonia. Reumatol Clin. 2020 Apr 16;S1699-258X(20)30044-9.
• [15] Anti-inflammatory therapy of dry eye. Ocul Surf. 2003 Jan;1(1):31-6.
• [16] Clinical pipeline report, company report or official report of Roche (2009).
• [17] 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.
• [18] 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.
• [19] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [20] Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
• [21] 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.
• [22] [Pharmacology of mycophenolate mofetil: recent data and clinical consequences]. Nephrologie. 2001;22(7):331-7.
• [23] ClinicalTrials.gov (NCT00087581) Study of Therapeutic Monitoring of Mycophenolate Mofetil (MMF/CellCept) After Kidney Transplantation
• [24] ClinicalTrials.gov (NCT00118742) Liver Spare the Nephron (STN) Study - A Study of CellCept (Mycophenolate Mofetil) and Sirolimus in Recipients of a Liver Transplant
• [25] ClinicalTrials.gov (NCT01659606) Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
• [26] ClinicalTrials.gov (NCT00040846) Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies
• [27] ClinicalTrials.gov (NCT00005799) Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer
• [28] ClinicalTrials.gov (NCT00420537) Shift to Everolimus (RAD) Kidney Sparing Study
• [29] ClinicalTrials.gov (NCT00008450) Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
• [30] ClinicalTrials.gov (NCT00008177) Radiolabeled Monoclonal Antibody Therapy, Fludarabine Phosphate, and Low-Dose Total-Body Irradiation Followed by Donor Stem Cell Transplant and Immunosuppression Therapy in Treating Older Patients With Advanced Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes
• [31] ClinicalTrials.gov (NCT00005851) Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Stage IV Kidney Cancer