Details of the Drug Combination

General Information of Drug Combination (ID: DCLOJN0)

• Drug Combination Name: Mesalazine + Mycophenolic acid
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Mesalazine (DMOL5IU): Small molecular drug
  Mycophenolic acid (DMRBMAU): N.A.
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 8.4
  Bliss Independence Score: 8.4
  Loewe Additivity Score: 10.06
  LHighest Single Agent (HSA) Score: 10.06

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Mesalazine

Disease Entry	ICD 11	Status	REF
Diverticulitis	N.A.	Approved	[2]
Proctitis	DB33.Z	Approved	[3]
Ulcerative colitis	DD71	Approved	[4]
Ulcerative proctosigmoiditis	N.A.	Approved	[5]

Mesalazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Inhibitor	[17]

Mesalazine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[18]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[19]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[19]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[19]

Mesalazine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[20]

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	[21]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[22]

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	[23]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[23]

References

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• [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] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [18] Transport studies with 5-aminosalicylate. Eur J Clin Pharmacol. 2006 Oct;62(10):871-5.
• [19] Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102.
• [20] NAT1 genotypes do not predict response to mesalamine in patients with ulcerative colitis. Z Gastroenterol. 2008 Mar;46(3):259-65.
• [21] 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.
• [22] 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.
• [23] 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.