General Information of Drug Combination (ID: DCCW9DE)

Drug Combination Name
Vandetanib DFN-15
Indication
Disease Entry Status REF
Glioma Investigative [1]
Component Drugs Vandetanib   DMRICNP DFN-15   DM3BF9B
Small molecular drug N.A.
High-throughput Screening Result Testing Cell Line: SF-268
Zero Interaction Potency (ZIP) Score: 2.89
Bliss Independence Score: 3.42
Loewe Additivity Score: 0.25
LHighest Single Agent (HSA) Score: 0.19

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Vandetanib
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Approved [2]
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 [4]
Proto-oncogene c-Ret (RET) TT4DXQT RET_HUMAN Inhibitor [4]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [4]
------------------------------------------------------------------------------------
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 [5]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [6]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [6]
------------------------------------------------------------------------------------
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 [7]
------------------------------------------------------------------------------------
Vandetanib Interacts with 34 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) OTLU040A RET_HUMAN Decreases Phosphorylation [8]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) OTKOZRZP PLOD2_HUMAN Increases Expression [9]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Increases Expression [9]
Insulin-induced gene 1 protein (INSIG1) OTZF5X1D INSI1_HUMAN Increases Expression [9]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L) OTJKOMXE BNI3L_HUMAN Increases Expression [9]
Protein FAM13A (FAM13A) OTZ6GN0Q FA13A_HUMAN Increases Expression [9]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Activity [10]
Phosphoglycerate kinase 1 (PGK1) OT6V1ICH PGK1_HUMAN Increases Expression [9]
Calbindin (CALB1) OTM7IXDG CALB1_HUMAN Increases Expression [9]
Prothymosin alpha (PTMA) OT2W4T1M PTMA_HUMAN Decreases Expression [9]
Trypsin-2 (PRSS2) OTOMVUWL TRY2_HUMAN Increases Expression [9]
Insulin-like growth factor-binding protein 1 (IGFBP1) OT6UQV2K IBP1_HUMAN Increases Expression [9]
Gamma-enolase (ENO2) OTRODL0T ENOG_HUMAN Increases Expression [9]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Increases Expression [9]
Mucin-1 (MUC1) OTHQI7IY MUC1_HUMAN Increases Expression [9]
Histone H1.2 (H1-2) OT0AVI4M H12_HUMAN Increases Expression [9]
Insulin-like growth factor-binding protein 3 (IGFBP3) OTIX63TX IBP3_HUMAN Increases Expression [9]
DNA mismatch repair protein Msh3 (MSH3) OTD3YPVL MSH3_HUMAN Decreases Expression [9]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [11]
Dual specificity protein phosphatase 1 (DUSP1) OTN6BR75 DUS1_HUMAN Increases Expression [9]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [12]
Pro-adrenomedullin (ADM) OT7T0TA4 ADML_HUMAN Increases Expression [9]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [12]
Collagen alpha-3(IV) chain (COL4A3) OT6SB8X5 CO4A3_HUMAN Increases Expression [9]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Expression [13]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [12]
Solute carrier family 2, facilitated glucose transporter member 14 (SLC2A14) OTBFIOVY GTR14_HUMAN Increases Expression [9]
Protein NDRG1 (NDRG1) OTVO66BO NDRG1_HUMAN Increases Expression [9]
TSC22 domain family protein 3 (TSC22D3) OT03UM03 T22D3_HUMAN Increases Expression [9]
Angiopoietin-related protein 4 (ANGPTL4) OTQL5SPX ANGL4_HUMAN Increases Expression [9]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [14]
Lysine-specific demethylase 3A (KDM3A) OTZYJ8VN KDM3A_HUMAN Increases Expression [9]
Hypoxia-inducible lipid droplet-associated protein (HILPDA) OTEID3ZM HLPDA_HUMAN Increases Expression [9]
Insulin-induced gene 2 protein (INSIG2) OTX4VY51 INSI2_HUMAN Increases Expression [9]
------------------------------------------------------------------------------------
⏷ Show the Full List of 34 DOT(s)
Indication(s) of DFN-15
Disease Entry ICD 11 Status REF
Migraine 8A80 Phase 3 [3]

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Colon adenocarcinoma DCWRJ3V COLO 205 Investigative [15]
Invasive ductal carcinoma DCEFF28 HS 578T Investigative [15]
Amelanotic melanoma DCYXQPQ MDA-MB-435 Investigative [1]
Chronic myelogenous leukemia DCULRGO K-562 Investigative [1]
Cutaneous melanoma DCM9ORN SK-MEL-5 Investigative [1]
Plasma cell myeloma DCHKH6P RPMI-8226 Investigative [1]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DrugCom(s)

References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
2 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).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 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.
5 Tyrosine kinase inhibitors and multidrug resistance proteins: interactions and biological consequences. Cancer Chemother Pharmacol. 2010 Jan;65(2):335-46.
6 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
7 FDA label of Vandetanib. The 2020 official website of the U.S. Food and Drug Administration.
8 The RET oncogene is a critical component of transcriptional programs associated with retinoic acid-induced differentiation in neuroblastoma. Mol Cancer Ther. 2007 Apr;6(4):1300-9.
9 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.
10 Anticancer effects of ZD6474, a VEGF receptor tyrosine kinase inhibitor, in gefitinib ("Iressa")-sensitive and resistant xenograft models. Cancer Sci. 2004 Dec;95(12):984-9. doi: 10.1111/j.1349-7006.2004.tb03187.x.
11 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
12 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.
13 Downregulation of hERG channel expression by tyrosine kinase inhibitors nilotinib and vandetanib predominantly contributes to arrhythmogenesis. Toxicol Lett. 2022 Jul 15;365:11-23. doi: 10.1016/j.toxlet.2022.06.001. Epub 2022 Jun 6.
14 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.
15 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.