General Information of Drug Combination (ID: DCF5JU8)

Drug Combination Name
Vandetanib Letrozole
Indication
Disease Entry Status REF
Non-small cell lung carcinoma Investigative [1]
Component Drugs Vandetanib   DMRICNP Letrozole   DMH07Y3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HOP-92
Zero Interaction Potency (ZIP) Score: 0.72
Bliss Independence Score: 3.57
Loewe Additivity Score: 5.85
LHighest Single Agent (HSA) Score: 5.78

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 [5]
Proto-oncogene c-Ret (RET) TT4DXQT RET_HUMAN Inhibitor [5]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [5]
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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 [6]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [7]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [7]
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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 [8]
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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 [9]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) OTKOZRZP PLOD2_HUMAN Increases Expression [10]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Increases Expression [10]
Insulin-induced gene 1 protein (INSIG1) OTZF5X1D INSI1_HUMAN Increases Expression [10]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L) OTJKOMXE BNI3L_HUMAN Increases Expression [10]
Protein FAM13A (FAM13A) OTZ6GN0Q FA13A_HUMAN Increases Expression [10]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Activity [11]
Phosphoglycerate kinase 1 (PGK1) OT6V1ICH PGK1_HUMAN Increases Expression [10]
Calbindin (CALB1) OTM7IXDG CALB1_HUMAN Increases Expression [10]
Prothymosin alpha (PTMA) OT2W4T1M PTMA_HUMAN Decreases Expression [10]
Trypsin-2 (PRSS2) OTOMVUWL TRY2_HUMAN Increases Expression [10]
Insulin-like growth factor-binding protein 1 (IGFBP1) OT6UQV2K IBP1_HUMAN Increases Expression [10]
Gamma-enolase (ENO2) OTRODL0T ENOG_HUMAN Increases Expression [10]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Increases Expression [10]
Mucin-1 (MUC1) OTHQI7IY MUC1_HUMAN Increases Expression [10]
Histone H1.2 (H1-2) OT0AVI4M H12_HUMAN Increases Expression [10]
Insulin-like growth factor-binding protein 3 (IGFBP3) OTIX63TX IBP3_HUMAN Increases Expression [10]
DNA mismatch repair protein Msh3 (MSH3) OTD3YPVL MSH3_HUMAN Decreases Expression [10]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [12]
Dual specificity protein phosphatase 1 (DUSP1) OTN6BR75 DUS1_HUMAN Increases Expression [10]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [13]
Pro-adrenomedullin (ADM) OT7T0TA4 ADML_HUMAN Increases Expression [10]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [13]
Collagen alpha-3(IV) chain (COL4A3) OT6SB8X5 CO4A3_HUMAN Increases Expression [10]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Expression [14]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [13]
Solute carrier family 2, facilitated glucose transporter member 14 (SLC2A14) OTBFIOVY GTR14_HUMAN Increases Expression [10]
Protein NDRG1 (NDRG1) OTVO66BO NDRG1_HUMAN Increases Expression [10]
TSC22 domain family protein 3 (TSC22D3) OT03UM03 T22D3_HUMAN Increases Expression [10]
Angiopoietin-related protein 4 (ANGPTL4) OTQL5SPX ANGL4_HUMAN Increases Expression [10]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [15]
Lysine-specific demethylase 3A (KDM3A) OTZYJ8VN KDM3A_HUMAN Increases Expression [10]
Hypoxia-inducible lipid droplet-associated protein (HILPDA) OTEID3ZM HLPDA_HUMAN Increases Expression [10]
Insulin-induced gene 2 protein (INSIG2) OTX4VY51 INSI2_HUMAN Increases Expression [10]
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⏷ Show the Full List of 34 DOT(s)
Indication(s) of Letrozole
Disease Entry ICD 11 Status REF
Estrogen-receptor positive breast cancer N.A. Approved [3]
Hormonally-responsive breast cancer 2C60-2C65 Approved [4]
Letrozole Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [16]
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Letrozole Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [17]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [18]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [19]
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Letrozole Interacts with 18 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [20]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [21]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Increases Oxidation [21]
Adenylate kinase isoenzyme 1 (AK1) OT614AR3 KAD1_HUMAN Increases ADR [22]
Dickkopf-related protein 1 (DKK1) OTRDLUSP DKK1_HUMAN Increases Expression [23]
Follitropin subunit beta (FSHB) OTGLS283 FSHB_HUMAN Increases Expression [24]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Increases Expression [24]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Decreases Expression [25]
Leukemia inhibitory factor (LIF) OTO46S5S LIF_HUMAN Increases Expression [23]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Decreases Expression [26]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [27]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [27]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [28]
Leukemia inhibitory factor receptor (LIFR) OT36W9O5 LIFR_HUMAN Increases Expression [23]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [25]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [27]
Lanosterol 14-alpha demethylase (CYP51A1) OTAYHG9C CP51A_HUMAN Decreases Activity [29]
Fibroblast growth factor 22 (FGF22) OTVIX6J0 FGF22_HUMAN Increases Expression [23]
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⏷ Show the Full List of 18 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Invasive ductal carcinoma DCG2336 BT-549 Investigative [30]
Invasive ductal carcinoma DCAT2GY HS 578T Investigative [30]
Amelanotic melanoma DC6OXI1 M14 Investigative [1]
Amelanotic melanoma DC1AQT8 MDA-MB-435 Investigative [1]
Cutaneous melanoma DCX4X0G SK-MEL-5 Investigative [1]
Cutaneous melanoma DCAAN46 SK-MEL-28 Investigative [1]
Glioma DC9GV90 SF-268 Investigative [1]
Plasma cell myeloma DCA0G8O RPMI-8226 Investigative [1]
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⏷ Show the Full List of 8 DrugCom(s)

References

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3 Letrozole FDA Label
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: 5209).
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8 FDA label of Vandetanib. The 2020 official website of the U.S. Food and Drug Administration.
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12 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.
13 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.
14 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.
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.
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18 Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients. Eur J Cancer. 1999 Feb;35(2):208-13.
19 Letrozole concentration is associated with CYP2A6 variation but not with arthralgia in patients with breast cancer. Breast Cancer Res Treat. 2018 Nov;172(2):371-379.
20 Aromatase inhibition: translation into a successful therapeutic approach. Clin Cancer Res. 2005 Apr 15;11(8):2809-21. doi: 10.1158/1078-0432.CCR-04-2187.
21 Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes. Xenobiotica. 2009 Nov;39(11):795-802. doi: 10.3109/00498250903171395.
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23 Clomiphene citrate versus letrozole: molecular analysis of the endometrium in women with polycystic ovary syndrome. Fertil Steril. 2011 Oct;96(4):1051-6. doi: 10.1016/j.fertnstert.2011.07.1092.
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28 Synergistic activity of letrozole and sorafenib on breast cancer cells. Breast Cancer Res Treat. 2010 Nov;124(1):79-88. doi: 10.1007/s10549-009-0714-5. Epub 2010 Jan 7.
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