Details of the Drug Combination

General Information of Drug Combination (ID: DCAH7MW)

• Drug Combination Name: Mycophenolic acid + Pamidronate
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Mycophenolic acid (DMRBMAU): N.A.
  Pamidronate (DMB4AVP): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 0.7
  Bliss Independence Score: 0.7
  Loewe Additivity Score: 1.97
  LHighest Single Agent (HSA) Score: 2.01

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	[15]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[16]

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	[17]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[17]

Indication(s) of Pamidronate

Disease Entry	ICD 11	Status	REF
Bone Paget disease	N.A.	Approved	[13]
Hypercalcaemia	5B91.0	Approved	[14]

Pamidronate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Geranyltranstransferase (FDPS)	TTIKWV4	FPPS_HUMAN	Inhibitor	[18]

Pamidronate Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[19]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Increases Expression	[19]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)	OTG7J4BP	PPBT_HUMAN	Increases Expression	[19]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[19]
Beta-2-microglobulin (B2M)	OTDWN6NX	B2MG_HUMAN	Decreases Expression	[19]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B)	OTQ4W7MT	TR11B_HUMAN	Increases Expression	[20]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[21]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[22]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[23]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[23]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Expression	[24]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[24]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[24]
Transforming protein RhoA (RHOA)	OT6YOJ9N	RHOA_HUMAN	Decreases Expression	[24]
Ras-related protein Rap-1A (RAP1A)	OT5RH6TI	RAP1A_HUMAN	Decreases Prenylation	[25]
Rho-associated protein kinase 1 (ROCK1)	OTSXYVW1	ROCK1_HUMAN	Decreases Expression	[24]
Fibroblast growth factor 23 (FGF23)	OTZT523D	FGF23_HUMAN	Decreases Expression	[26]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases Response To Substance	[27]

References

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• [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.
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• [13] Pamidronate FDA Label
• [14] 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: 7259).
• [15] 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.
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• [17] 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.
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• [19] Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment. Calcif Tissue Int. 2001 May;68(5):285-90.
• [20] Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts. Biochem Biophys Res Commun. 2002 Mar 1;291(3):680-6. doi: 10.1006/bbrc.2002.6510.
• [21] An in vitro and in vivo study of cytokines in the acute-phase response associated with bisphosphonates. Calcif Tissue Int. 1997 Nov;61(5):386-92. doi: 10.1007/s002239900353.
• [22] Expression profile and synthesis of different collagen types I, II, III, and V of human gingival fibroblasts, osteoblasts, and SaOS-2 cells after bisphosphonate treatment. Clin Oral Investig. 2010 Feb;14(1):51-8. doi: 10.1007/s00784-009-0312-2. Epub 2009 Jul 14.
• [23] Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer. 2000 Apr;82(8):1459-68. doi: 10.1054/bjoc.1999.1131.
• [24] Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma. J Hepatol. 2006 Jan;44(1):142-50. doi: 10.1016/j.jhep.2005.09.022. Epub 2005 Nov 9.
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