General Information of Drug Combination (ID: DCL8KTM)

Drug Combination Name
Bleomycin Mepacrine
Indication
Disease Entry Status REF
Papillary renal cell carcinoma Investigative [1]
Component Drugs Bleomycin   DMNER5S Mepacrine   DMU8L7C
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: ACHN
Zero Interaction Potency (ZIP) Score: 2.11
Bliss Independence Score: 3.65
Loewe Additivity Score: 2.02
LHighest Single Agent (HSA) Score: 3.45

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Bleomycin
Disease Entry ICD 11 Status REF
Cervical cancer 2C77.0 Approved [2]
Head and neck cancer 2D42 Approved [2]
Hodgkin lymphoma 2B30 Approved [3]
Penile cancer N.A. Approved [2]
Testicular germ cell tumor N.A. Approved [2]
Classic Hodgkin lymphoma N.A. Investigative [2]
Follicular lymphoma 2A80 Investigative [2]
Bleomycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Breaker [9]
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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 [10]
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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 [11]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Increases Expression [12]
Catalase (CAT) OTHEBX9R CATA_HUMAN Increases Expression [12]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [12]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Increases Expression [13]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Increases Expression [13]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [13]
C-X-C motif chemokine 2 (CXCL2) OTEJCYMY CXCL2_HUMAN Increases Expression [13]
Mucin-5AC (MUC5AC) OTJV8O04 MUC5A_HUMAN Increases Expression [13]
Proheparin-binding EGF-like growth factor (HBEGF) OTLU00JS HBEGF_HUMAN Increases Expression [13]
Transmembrane protein 250 (TMEM250) OTLJ4G5G TM250_HUMAN Increases Expression [5]
Suppressor of cytokine signaling 1 (SOCS1) OTWA9KFU SOCS1_HUMAN Decreases Expression [14]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Phosphorylation [15]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [6]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [16]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [6]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Increases Expression [6]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [17]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [6]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [18]
Cathepsin S (CTSS) OT3PXIPM CATS_HUMAN Increases Expression [19]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [20]
Max-interacting protein 1 (MXI1) OTUQ9E0D MXI1_HUMAN Decreases Expression [5]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Increases Expression [6]
Unconventional myosin-Ie (MYO1E) OTM9YSIZ MYO1E_HUMAN Decreases Expression [5]
Transcription intermediary factor 1-beta (TRIM28) OTE38OBF TIF1B_HUMAN Increases Phosphorylation [15]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Phosphorylation [15]
Structural maintenance of chromosomes protein 1A (SMC1A) OT9ZMRK9 SMC1A_HUMAN Increases Phosphorylation [15]
7SK snRNA methylphosphate capping enzyme (MEPCE) OTRBQEYP MEPCE_HUMAN Increases Expression [5]
Transmembrane protein 87A (TMEM87A) OT8ATDVX TM87A_HUMAN Increases Expression [5]
Terminal nucleotidyltransferase 4B (TENT4B) OTUF6FWW PAPD5_HUMAN Decreases Expression [5]
Lipase member H (LIPH) OTRGYLKL LIPH_HUMAN Decreases Expression [5]
Abasic site processing protein HMCES (HMCES) OTVRDL6U HMCES_HUMAN Decreases Expression [5]
Small integral membrane protein 14 (SMIM14) OT47IF19 SIM14_HUMAN Decreases Expression [5]
Kelch-like protein 42 (KLHL42) OTK6WARI KLH42_HUMAN Increases Expression [5]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2) OT9I1XUO CEIP2_HUMAN Decreases Expression [5]
ERBB receptor feedback inhibitor 1 (ERRFI1) OT7VZ2IZ ERRFI_HUMAN Decreases Expression [5]
Transmembrane and coiled-coil domain protein 3 (TMCC3) OTAIQ6V6 TMCC3_HUMAN Decreases Expression [5]
Lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5) OT27CCUF SIAT9_HUMAN Decreases Expression [5]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [21]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Affects Response To Substance [22]
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⏷ Show the Full List of 41 DOT(s)
Indication(s) of Mepacrine
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [4]
Mepacrine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Phospholipase A2 (PLA2G1B) TT9V5JH PA21B_HUMAN Inhibitor [4]
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Mepacrine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [23]
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Mepacrine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [24]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [24]
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Mepacrine Interacts with 22 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [25]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [26]
Zinc finger protein GLI1 (GLI1) OT1BTAJO GLI1_HUMAN Decreases Expression [25]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [27]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) OTSBQR6D PLCG1_HUMAN Decreases Phosphorylation [28]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [25]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [27]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [27]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [25]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Decreases Phosphorylation [28]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [29]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [25]
Casein kinase I isoform alpha (CSNK1A1) OTJ6O1IC KC1A_HUMAN Increases Expression [25]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Expression [25]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [27]
Focal adhesion kinase 1 (PTK2) OT3Q1JDY FAK1_HUMAN Decreases Phosphorylation [28]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [27]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [30]
Forkhead box protein P3 (FOXP3) OTA9Z9OC FOXP3_HUMAN Increases Expression [27]
F-box/WD repeat-containing protein 1A (BTRC) OT2EZDGR FBW1A_HUMAN Decreases Expression [27]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Metabolism [24]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [24]
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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
Adenocarcinoma DCV7GP8 HT29 Investigative [31]
Mixed endometrioid and clear cell carcinoma DCPP8LW IGROV1 Investigative [31]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Bleomycin FDA Label
3 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
4 Involvement of protein kinase C activation in L-leucine-induced stimulation of protein synthesis in l6 myotubes. Cytotechnology. 2003 Nov;43(1-3):97-103.
5 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.
6 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.
7 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.
8 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.
9 Bleomycin and talisomycin sequence-specific strand scission of DNA: a mechanism of double-strand cleavage. Cancer Res. 1982 Jul;42(7):2779-85.
10 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.
11 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.
12 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.
13 Agents associated with lung inflammation induce similar responses in NCI-H292 lung epithelial cells. Toxicol In Vitro. 2008 Oct;22(7):1782-8.
14 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.
15 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.
16 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.
17 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.
18 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.
19 Radiation-induced cathepsin S is involved in radioresistance. Int J Cancer. 2009 Apr 15;124(8):1794-801. doi: 10.1002/ijc.24095.
20 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.
21 Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
22 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.
23 Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 2005 Jan 15;385(Pt 2):419-26.
24 Quinacrine is mainly metabolized to mono-desethyl quinacrine by CYP3A4/5 and its brain accumulation is limited by P-glycoprotein. Drug Metab Dispos. 2006 Jul;34(7):1136-44.
25 Nanoquinacrine caused apoptosis in oral cancer stem cells by disrupting the interaction between GLI1 and catenin through activation of GSK3. Toxicol Appl Pharmacol. 2017 Sep 1;330:53-64. doi: 10.1016/j.taap.2017.07.008. Epub 2017 Jul 15.
26 High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter. Carcinogenesis. 2002 Jun;23(6):949-57. doi: 10.1093/carcin/23.6.949.
27 Quinacrine induces the apoptosis of human leukemia U937 cells through FOXP3/miR-183/-TrCP/SP1 axis-mediated BAX upregulation. Toxicol Appl Pharmacol. 2017 Nov 1;334:35-46. doi: 10.1016/j.taap.2017.08.019. Epub 2017 Sep 1.
28 Quinacrine is active in preclinical models of glioblastoma through suppressing angiogenesis, inducing oxidative stress and activating AMPK. Toxicol In Vitro. 2022 Sep;83:105420. doi: 10.1016/j.tiv.2022.105420. Epub 2022 Jun 17.
29 Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action. Arch Toxicol. 2021 Jan;95(1):321-336. doi: 10.1007/s00204-020-02902-3. Epub 2020 Sep 10.
30 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
31 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.