Details of the Drug Combination

General Information of Drug Combination (ID: DC3ZEMK)

Drug Combination Name

Pazopanib Tivantinib

Indication

Disease Entry	Status	REF
Solid Tumor	Phase 1	[1]

Component Drugs

Pazopanib DMF57DM

Tivantinib DMNVP8Q

N.A.

Small molecular drug

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

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]
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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]
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⏷ Show the Full List of 6 DOT(s)

Indication(s) of Tivantinib

Disease Entry	ICD 11	Status	REF
Hepatocellular carcinoma	2C12.02	Phase 3	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 3	[3]

Tivantinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Inhibitor	[3]
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References

1	ClinicalTrials.gov (NCT01468922) Pazopanib and ARQ 197 for Advanced Solid Tumors
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 7948).
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.