General Information of Drug Combination (ID: DCRC964)

Drug Combination Name
Vandetanib Bleomycin
Indication
Disease Entry Status REF
Clear cell renal cell carcinoma 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: CAKI-1
Zero Interaction Potency (ZIP) Score: 5.38
Bliss Independence Score: 4.42
Loewe Additivity Score: 8.34
LHighest Single Agent (HSA) Score: 10.89

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 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 [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]
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]
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]
Histone H1.2 (H1-2) OT0AVI4M H12_HUMAN Increases Expression [9]
DNA mismatch repair protein Msh3 (MSH3) OTD3YPVL MSH3_HUMAN Decreases Expression [9]
Pro-adrenomedullin (ADM) OT7T0TA4 ADML_HUMAN Increases Expression [9]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [10]
Collagen alpha-3(IV) chain (COL4A3) OT6SB8X5 CO4A3_HUMAN Increases Expression [9]
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]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [11]
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]
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⏷ Show the Full List of 22 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 [16]
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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 [17]
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Bleomycin Interacts with 23 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [18]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Increases Expression [19]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [19]
Mucin-5AC (MUC5AC) OTJV8O04 MUC5A_HUMAN Increases Expression [19]
Transmembrane protein 250 (TMEM250) OTLJ4G5G TM250_HUMAN Increases Expression [12]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Phosphorylation [20]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [13]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [21]
Max-interacting protein 1 (MXI1) OTUQ9E0D MXI1_HUMAN Decreases Expression [12]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Increases Expression [13]
Unconventional myosin-Ie (MYO1E) OTM9YSIZ MYO1E_HUMAN Decreases Expression [12]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Phosphorylation [20]
Structural maintenance of chromosomes protein 1A (SMC1A) OT9ZMRK9 SMC1A_HUMAN Increases Phosphorylation [20]
7SK snRNA methylphosphate capping enzyme (MEPCE) OTRBQEYP MEPCE_HUMAN Increases Expression [12]
Transmembrane protein 87A (TMEM87A) OT8ATDVX TM87A_HUMAN Increases Expression [12]
Lipase member H (LIPH) OTRGYLKL LIPH_HUMAN Decreases Expression [12]
Abasic site processing protein HMCES (HMCES) OTVRDL6U HMCES_HUMAN Decreases Expression [12]
Small integral membrane protein 14 (SMIM14) OT47IF19 SIM14_HUMAN Decreases Expression [12]
Kelch-like protein 42 (KLHL42) OTK6WARI KLH42_HUMAN Increases Expression [12]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2) OT9I1XUO CEIP2_HUMAN Decreases Expression [12]
ERBB receptor feedback inhibitor 1 (ERRFI1) OT7VZ2IZ ERRFI_HUMAN Decreases Expression [12]
Transmembrane and coiled-coil domain protein 3 (TMCC3) OTAIQ6V6 TMCC3_HUMAN Decreases Expression [12]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [22]
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⏷ Show the Full List of 23 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast adenocarcinoma DC542BR MDA-MB-468 Investigative [23]
Colon carcinoma DCJO42M KM12 Investigative [23]
Adenocarcinoma DCPLPMI A549 Investigative [1]
Adenocarcinoma DCEAIMB HT29 Investigative [1]
Adenocarcinoma DC0NDF7 SW-620 Investigative [1]
Adenocarcinoma DCKFYR9 HCT-15 Investigative [1]
Adenocarcinoma DCPU1BF HCC-2998 Investigative [1]
Adult acute myeloid leukemia DC1HJYQ HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DCDXD6A MOLT-4 Investigative [1]
Astrocytoma DCZ85NY SNB-19 Investigative [1]
Chronic myelogenous leukemia DCWDW4D K-562 Investigative [1]
Clear cell renal cell carcinoma DCLS3QE A498 Investigative [1]
Clear cell renal cell carcinoma DCJNWMV 786-0 Investigative [1]
Glioma DCQK4N1 SF-539 Investigative [1]
Glioma DCV45FC SF-295 Investigative [1]
High grade ovarian serous adenocarcinoma DCTGAJQ OVCAR-8 Investigative [1]
Large cell lung carcinoma DCINPM3 NCI-H460 Investigative [1]
Lung adenocarcinoma DCLUJ8N MDA-MB-231 Investigative [1]
Lung adenocarcinoma DCB9YS4 EKVX Investigative [1]
Malignant melanoma DCRSRV7 LOX IMVI Investigative [1]
Mixed endometrioid and clear cell carcinoma DCQTCJ3 IGROV1 Investigative [1]
Non-small cell lung carcinoma DCREE1I HOP-92 Investigative [1]
Renal cell carcinoma DCPJUIG SN12C Investigative [1]
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⏷ Show the Full List of 23 DrugCom(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
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 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 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.
11 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.
12 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.
13 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.
14 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.
15 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.
16 Bleomycin and talisomycin sequence-specific strand scission of DNA: a mechanism of double-strand cleavage. Cancer Res. 1982 Jul;42(7):2779-85.
17 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.
18 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.
19 Agents associated with lung inflammation induce similar responses in NCI-H292 lung epithelial cells. Toxicol In Vitro. 2008 Oct;22(7):1782-8.
20 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.
21 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.
22 Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
23 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165