Details of the Drug Combination

General Information of Drug Combination (ID: DCENZFR)

Drug Combination Name
Cabozantinib Vandetanib
Indication
Disease Entry Status REF
Medullary Thyroid Cancer Phase 3 [1]
Component Drugs Cabozantinib   DMIYDT4 Vandetanib   DMRICNP
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Cabozantinib
Disease Entry ICD 11 Status REF
Medullary thyroid gland carcinoma N.A. Approved [2]
Thyroid cancer 2D10 Approved [3]
Ovarian cancer 2C73 Phase 2 [3]
Cabozantinib Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Proto-oncogene c-Met (MET) TTNDSF4 MET_HUMAN Inhibitor [5]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [5]
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Cabozantinib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [7]
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Cabozantinib Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Decreases Phosphorylation [8]
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Indication(s) of Vandetanib
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Approved [4]
Vandetanib Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [9]
Proto-oncogene c-Ret (RET) TT4DXQT RET_HUMAN Inhibitor [9]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [9]
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Vandetanib Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [10]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [11]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [11]
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Vandetanib Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
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Vandetanib Interacts with 22 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) OTKOZRZP PLOD2_HUMAN Increases Expression [13]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Increases Expression [13]
Insulin-induced gene 1 protein (INSIG1) OTZF5X1D INSI1_HUMAN Increases Expression [13]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L) OTJKOMXE BNI3L_HUMAN Increases Expression [13]
Protein FAM13A (FAM13A) OTZ6GN0Q FA13A_HUMAN Increases Expression [13]
Phosphoglycerate kinase 1 (PGK1) OT6V1ICH PGK1_HUMAN Increases Expression [13]
Calbindin (CALB1) OTM7IXDG CALB1_HUMAN Increases Expression [13]
Prothymosin alpha (PTMA) OT2W4T1M PTMA_HUMAN Decreases Expression [13]
Trypsin-2 (PRSS2) OTOMVUWL TRY2_HUMAN Increases Expression [13]
Gamma-enolase (ENO2) OTRODL0T ENOG_HUMAN Increases Expression [13]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Increases Expression [13]
Histone H1.2 (H1-2) OT0AVI4M H12_HUMAN Increases Expression [13]
DNA mismatch repair protein Msh3 (MSH3) OTD3YPVL MSH3_HUMAN Decreases Expression [13]
Pro-adrenomedullin (ADM) OT7T0TA4 ADML_HUMAN Increases Expression [13]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [14]
Collagen alpha-3(IV) chain (COL4A3) OT6SB8X5 CO4A3_HUMAN Increases Expression [13]
Solute carrier family 2, facilitated glucose transporter member 14 (SLC2A14) OTBFIOVY GTR14_HUMAN Increases Expression [13]
Protein NDRG1 (NDRG1) OTVO66BO NDRG1_HUMAN Increases Expression [13]
TSC22 domain family protein 3 (TSC22D3) OT03UM03 T22D3_HUMAN Increases Expression [13]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [15]
Hypoxia-inducible lipid droplet-associated protein (HILPDA) OTEID3ZM HLPDA_HUMAN Increases Expression [13]
Insulin-induced gene 2 protein (INSIG2) OTX4VY51 INSI2_HUMAN Increases Expression [13]
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⏷ Show the Full List of 22 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Thyroid Cancer DC6PJ87 N. A. Phase 2 [16]
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References

1 ClinicalTrials.gov (NCT04760288) A Study of Pralsetinib Versus Standard of Care (SOC) for Treatment of RET-Mutated Medullary Thyroid Cancer (MTC).
2 Cabozantinib 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: 5887).
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. (Ligand id: 5717).
5 Clinical pipeline report, company report or official report of Exelixis (2011).
6 Practical management of adverse events associated with cabozantinib treatment in patients with renal-cell carcinoma. Onco Targets Ther. 2017 Oct 19;10:5053-5064.
7 FDA Label of Cabozantinib. The 2020 official website of the U.S. Food and Drug Administration.
8 ROS-dependent DNA damage contributes to crizotinib-induced hepatotoxicity via the apoptotic pathway. Toxicol Appl Pharmacol. 2019 Nov 15;383:114768. doi: 10.1016/j.taap.2019.114768. Epub 2019 Oct 19.
9 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
10 Tyrosine kinase inhibitors and multidrug resistance proteins: interactions and biological consequences. Cancer Chemother Pharmacol. 2010 Jan;65(2):335-46.
11 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
12 FDA label of Vandetanib. The 2020 official website of the U.S. Food and Drug Administration.
13 ZD6474 inhibits tumor growth and intraperitoneal dissemination in a highly metastatic orthotopic gastric cancer model. Int J Cancer. 2006 Jan 15;118(2):483-9. doi: 10.1002/ijc.21340.
14 Autophagy inhibition induces enhanced proapoptotic effects of ZD6474 in glioblastoma. Br J Cancer. 2013 Jul 9;109(1):164-71. doi: 10.1038/bjc.2013.306. Epub 2013 Jun 25.
15 A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci. 2014 Jan;137(1):76-90. doi: 10.1093/toxsci/kft239. Epub 2013 Oct 23.
16 ClinicalTrials.gov (NCT03630120) Adaptive Tyrosine Kinase Inhibitor (TKI) Therapy In Patients With Thyroid Cancer