General Information of Drug Combination (ID: DC542BR)

Drug Combination Name
Vandetanib Bleomycin
Indication
Disease Entry Status REF
Breast adenocarcinoma Investigative [1]
Component Drugs Vandetanib   DMRICNP Bleomycin   DMNER5S
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: MDA-MB-468
Zero Interaction Potency (ZIP) Score: 7.69
Bliss Independence Score: 10.07
Loewe Additivity Score: 11.24
LHighest Single Agent (HSA) Score: 11.51

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 Bleomycin
Disease Entry ICD 11 Status REF
Cervical cancer 2C77.0 Approved [3]
Head and neck cancer 2D42 Approved [3]
Hodgkin lymphoma 2B30 Approved [4]
Penile cancer N.A. Approved [3]
Testicular germ cell tumor N.A. Approved [3]
Classic Hodgkin lymphoma N.A. Investigative [3]
Follicular lymphoma 2A80 Investigative [3]
Bleomycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Breaker [20]
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Bleomycin Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Bleomycin hydrolase (BLMH) DECH1VP BLMH_HUMAN Metabolism [21]
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Bleomycin Interacts with 41 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bleomycin hydrolase (BLMH) OT2QPWQJ BLMH_HUMAN Affects Response To Substance [22]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Increases Expression [23]
Catalase (CAT) OTHEBX9R CATA_HUMAN Increases Expression [23]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [23]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Increases Expression [24]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Increases Expression [24]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [24]
C-X-C motif chemokine 2 (CXCL2) OTEJCYMY CXCL2_HUMAN Increases Expression [24]
Mucin-5AC (MUC5AC) OTJV8O04 MUC5A_HUMAN Increases Expression [24]
Proheparin-binding EGF-like growth factor (HBEGF) OTLU00JS HBEGF_HUMAN Increases Expression [24]
Transmembrane protein 250 (TMEM250) OTLJ4G5G TM250_HUMAN Increases Expression [16]
Suppressor of cytokine signaling 1 (SOCS1) OTWA9KFU SOCS1_HUMAN Decreases Expression [25]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Phosphorylation [26]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [17]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [27]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [17]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Increases Expression [17]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [28]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [17]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [29]
Cathepsin S (CTSS) OT3PXIPM CATS_HUMAN Increases Expression [30]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [31]
Max-interacting protein 1 (MXI1) OTUQ9E0D MXI1_HUMAN Decreases Expression [16]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Increases Expression [17]
Unconventional myosin-Ie (MYO1E) OTM9YSIZ MYO1E_HUMAN Decreases Expression [16]
Transcription intermediary factor 1-beta (TRIM28) OTE38OBF TIF1B_HUMAN Increases Phosphorylation [26]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Phosphorylation [26]
Structural maintenance of chromosomes protein 1A (SMC1A) OT9ZMRK9 SMC1A_HUMAN Increases Phosphorylation [26]
7SK snRNA methylphosphate capping enzyme (MEPCE) OTRBQEYP MEPCE_HUMAN Increases Expression [16]
Transmembrane protein 87A (TMEM87A) OT8ATDVX TM87A_HUMAN Increases Expression [16]
Terminal nucleotidyltransferase 4B (TENT4B) OTUF6FWW PAPD5_HUMAN Decreases Expression [16]
Lipase member H (LIPH) OTRGYLKL LIPH_HUMAN Decreases Expression [16]
Abasic site processing protein HMCES (HMCES) OTVRDL6U HMCES_HUMAN Decreases Expression [16]
Small integral membrane protein 14 (SMIM14) OT47IF19 SIM14_HUMAN Decreases Expression [16]
Kelch-like protein 42 (KLHL42) OTK6WARI KLH42_HUMAN Increases Expression [16]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2) OT9I1XUO CEIP2_HUMAN Decreases Expression [16]
ERBB receptor feedback inhibitor 1 (ERRFI1) OT7VZ2IZ ERRFI_HUMAN Decreases Expression [16]
Transmembrane and coiled-coil domain protein 3 (TMCC3) OTAIQ6V6 TMCC3_HUMAN Decreases Expression [16]
Lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5) OT27CCUF SIAT9_HUMAN Decreases Expression [16]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [32]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Affects Response To Substance [33]
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⏷ Show the Full List of 41 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Colon carcinoma DCJO42M KM12 Investigative [1]
Adenocarcinoma DCPLPMI A549 Investigative [34]
Adenocarcinoma DCEAIMB HT29 Investigative [34]
Adenocarcinoma DC0NDF7 SW-620 Investigative [34]
Adenocarcinoma DCKFYR9 HCT-15 Investigative [34]
Adenocarcinoma DCPU1BF HCC-2998 Investigative [34]
Adult acute myeloid leukemia DC1HJYQ HL-60(TB) Investigative [34]
Adult T acute lymphoblastic leukemia DCDXD6A MOLT-4 Investigative [34]
Astrocytoma DCZ85NY SNB-19 Investigative [34]
Chronic myelogenous leukemia DCWDW4D K-562 Investigative [34]
Clear cell renal cell carcinoma DCLS3QE A498 Investigative [34]
Clear cell renal cell carcinoma DCJNWMV 786-0 Investigative [34]
Clear cell renal cell carcinoma DCRC964 CAKI-1 Investigative [34]
Glioma DCQK4N1 SF-539 Investigative [34]
Glioma DCV45FC SF-295 Investigative [34]
High grade ovarian serous adenocarcinoma DCTGAJQ OVCAR-8 Investigative [34]
Large cell lung carcinoma DCINPM3 NCI-H460 Investigative [34]
Lung adenocarcinoma DCLUJ8N MDA-MB-231 Investigative [34]
Lung adenocarcinoma DCB9YS4 EKVX Investigative [34]
Malignant melanoma DCRSRV7 LOX IMVI Investigative [34]
Mixed endometrioid and clear cell carcinoma DCQTCJ3 IGROV1 Investigative [34]
Non-small cell lung carcinoma DCREE1I HOP-92 Investigative [34]
Renal cell carcinoma DCPJUIG SN12C Investigative [34]
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⏷ Show the Full List of 23 DrugCom(s)

References

1 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.
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 Bleomycin FDA Label
4 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
5 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.
6 Tyrosine kinase inhibitors and multidrug resistance proteins: interactions and biological consequences. Cancer Chemother Pharmacol. 2010 Jan;65(2):335-46.
7 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
8 FDA label of Vandetanib. The 2020 official website of the U.S. Food and Drug Administration.
9 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.
10 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.
11 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.
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.
16 Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
17 Pulmonary fibrosis model using micro-CT analyzable human PSC-derived alveolar organoids containing alveolar macrophage-like cells. Cell Biol Toxicol. 2022 Aug;38(4):557-575. doi: 10.1007/s10565-022-09698-1. Epub 2022 Mar 10.
18 An antisense oligonucleotide targeted to human Ku86 messenger RNA sensitizes M059K malignant glioma cells to ionizing radiation, bleomycin, and etoposide but not DNA cross-linking agents. Cancer Res. 2002 Oct 15;62(20):5888-96.
19 XRCC1 deficiency sensitizes human lung epithelial cells to genotoxicity by crocidolite asbestos and Libby amphibole. Environ Health Perspect. 2010 Dec;118(12):1707-13. doi: 10.1289/ehp.1002312. Epub 2010 Aug 11.
20 Bleomycin and talisomycin sequence-specific strand scission of DNA: a mechanism of double-strand cleavage. Cancer Res. 1982 Jul;42(7):2779-85.
21 The C-terminus of human bleomycin hydrolase is required for protection against bleomycin-induced chromosomal damage. Mutat Res. 1998 Oct 12;421(1):1-7.
22 Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity. Carcinogenesis. 2002 Jun;23(6):1003-8. doi: 10.1093/carcin/23.6.1003.
23 Age-dependent basal level and induction capacity of copper-zinc and manganese superoxide dismutase and other scavenging enzyme activities in leukocytes from young and elderly adults. Am J Pathol. 1993 Jul;143(1):312-20.
24 Agents associated with lung inflammation induce similar responses in NCI-H292 lung epithelial cells. Toxicol In Vitro. 2008 Oct;22(7):1782-8.
25 Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.
26 Direct activation of ATM by resveratrol under oxidizing conditions. PLoS One. 2014 Jun 16;9(6):e97969. doi: 10.1371/journal.pone.0097969. eCollection 2014.
27 Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure. J Immunol. 1993 May 1;150(9):4188-96.
28 Synergistic anticancer activity of dietary tea polyphenols and bleomycin hydrochloride in human cervical cancer cell: Caspase-dependent and independent apoptotic pathways. Chem Biol Interact. 2016 Mar 5;247:1-10. doi: 10.1016/j.cbi.2016.01.012. Epub 2016 Jan 29.
29 Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15.
30 Radiation-induced cathepsin S is involved in radioresistance. Int J Cancer. 2009 Apr 15;124(8):1794-801. doi: 10.1002/ijc.24095.
31 Bleomycin-induced nuclear factor-kappaB activation in human bronchial epithelial cells involves the phosphorylation of glycogen synthase kinase 3beta. Toxicol Lett. 2009 Jun 22;187(3):194-200. doi: 10.1016/j.toxlet.2009.02.023. Epub 2009 Mar 13.
32 Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
33 DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol. 2008 Jan;28(2):752-71. doi: 10.1128/MCB.01799-07. Epub 2007 Nov 8.
34 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.