Details of the Drug Combination

General Information of Drug Combination (ID: DCWOC84)

• Drug Combination Name: Pazopanib + Moxifloxacin
• Indication: Carcinoma, Renal Cell; Status: Phase 1 [1]
• Component Drugs:
  Pazopanib (DMF57DM): N.A.
  Moxifloxacin (DMU8V4S): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Pazopanib Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[5]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[6]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[5]

Pazopanib Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[7]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[8]
Myeloblastin (PRTN3)	OT72MHP7	PRTN3_HUMAN	Increases Expression	[9]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[10]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[10]
HLA class I histocompatibility antigen protein P5 (HCP5)	OTV0YRI8	HCP5_HUMAN	Increases ADR	[11]

Indication(s) of Moxifloxacin

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[2]
Mycoplasma pneumoniae pneumonia	N.A.	Approved	[3]
Peritonitis	N.A.	Approved	[3]
Pneumonic plague	N.A.	Approved	[3]
Septicemic plague	N.A.	Approved	[3]
Staphylococcal pneumonia	N.A.	Approved	[3]
Staphylococcus aureus infection	N.A.	Approved	[3]
Streptococcal pneumonia	N.A.	Approved	[3]
Tuberculosis	1B10-1B14	Approved	[3]
Pneumonia caused by chlamydia	N.A.	Investigative	[3]
Pneumonia due to Klebsiella pneumoniae	CA40.03	Investigative	[3]

Moxifloxacin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial DNA gyrase (Bact gyrase)	TTN6J5F	GYRA_STAAU; GYRB_STAAU	Modulator	[12]
Staphylococcus Topoisomerase IV (Stap-coc parC)	TTIXTO3	PARC_STAAS	Modulator	[12]

References

• [1] ClinicalTrials.gov (NCT00861029) VEG111485: A QTc Study of Pazopanib
• [2] Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
• [3] Moxifloxacin FDA Label
• [4] Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. Br J Cancer. 2010 Apr 27;102(9):1371-7. doi: 10.1038/sj.bjc.6605653. Epub 2010 Apr 13.
• [5] Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35.
• [6] Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54.
• [7] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [8] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [9] Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events. Toxicol In Vitro. 2021 Mar;71:105063. doi: 10.1016/j.tiv.2020.105063. Epub 2020 Dec 1.
• [10] MEK inhibition abrogates sunitinib resistance in a renal cell carcinoma patient-derived xenograft model. Br J Cancer. 2016 Oct 11;115(8):920-928. doi: 10.1038/bjc.2016.263. Epub 2016 Aug 25.
• [11] HLA-B*57:01 Confers Susceptibility to Pazopanib-Associated Liver Injury in Patients with Cancer. Clin Cancer Res. 2016 Mar 15;22(6):1371-7. doi: 10.1158/1078-0432.CCR-15-2044. Epub 2015 Nov 6.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.