General Information of Drug Combination (ID: DCB8ZXY)

Drug Combination Name
Bleomycin Busulfan
Indication
Disease Entry Status REF
Anaplastic large cell lymphoma Investigative [1]
Component Drugs Bleomycin   DMNER5S Busulfan   DMXYJ9C
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SR
Zero Interaction Potency (ZIP) Score: 3.66
Bliss Independence Score: 4.05
Loewe Additivity Score: 0.14
LHighest Single Agent (HSA) Score: 5.97

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 [10]
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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 [11]
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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 [12]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Increases Expression [13]
Catalase (CAT) OTHEBX9R CATA_HUMAN Increases Expression [13]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [13]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Increases Expression [14]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Increases Expression [14]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [14]
C-X-C motif chemokine 2 (CXCL2) OTEJCYMY CXCL2_HUMAN Increases Expression [14]
Mucin-5AC (MUC5AC) OTJV8O04 MUC5A_HUMAN Increases Expression [14]
Proheparin-binding EGF-like growth factor (HBEGF) OTLU00JS HBEGF_HUMAN Increases Expression [14]
Transmembrane protein 250 (TMEM250) OTLJ4G5G TM250_HUMAN Increases Expression [6]
Suppressor of cytokine signaling 1 (SOCS1) OTWA9KFU SOCS1_HUMAN Decreases Expression [15]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Phosphorylation [16]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [7]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [17]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [7]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Increases Expression [7]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [18]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [7]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [19]
Cathepsin S (CTSS) OT3PXIPM CATS_HUMAN Increases Expression [20]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [21]
Max-interacting protein 1 (MXI1) OTUQ9E0D MXI1_HUMAN Decreases Expression [6]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Increases Expression [7]
Unconventional myosin-Ie (MYO1E) OTM9YSIZ MYO1E_HUMAN Decreases Expression [6]
Transcription intermediary factor 1-beta (TRIM28) OTE38OBF TIF1B_HUMAN Increases Phosphorylation [16]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Phosphorylation [16]
Structural maintenance of chromosomes protein 1A (SMC1A) OT9ZMRK9 SMC1A_HUMAN Increases Phosphorylation [16]
7SK snRNA methylphosphate capping enzyme (MEPCE) OTRBQEYP MEPCE_HUMAN Increases Expression [6]
Transmembrane protein 87A (TMEM87A) OT8ATDVX TM87A_HUMAN Increases Expression [6]
Terminal nucleotidyltransferase 4B (TENT4B) OTUF6FWW PAPD5_HUMAN Decreases Expression [6]
Lipase member H (LIPH) OTRGYLKL LIPH_HUMAN Decreases Expression [6]
Abasic site processing protein HMCES (HMCES) OTVRDL6U HMCES_HUMAN Decreases Expression [6]
Small integral membrane protein 14 (SMIM14) OT47IF19 SIM14_HUMAN Decreases Expression [6]
Kelch-like protein 42 (KLHL42) OTK6WARI KLH42_HUMAN Increases Expression [6]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2) OT9I1XUO CEIP2_HUMAN Decreases Expression [6]
ERBB receptor feedback inhibitor 1 (ERRFI1) OT7VZ2IZ ERRFI_HUMAN Decreases Expression [6]
Transmembrane and coiled-coil domain protein 3 (TMCC3) OTAIQ6V6 TMCC3_HUMAN Decreases Expression [6]
Lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5) OT27CCUF SIAT9_HUMAN Decreases Expression [6]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [22]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Affects Response To Substance [23]
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⏷ Show the Full List of 41 DOT(s)
Indication(s) of Busulfan
Disease Entry ICD 11 Status REF
Chronic myelogenous leukaemia 2A20.0 Approved [4]
Hematologic disease 3C0Z Approved [4]
Immunodeficiency 4A00-4A85 Approved [4]
Leukemia N.A. Approved [4]
Myeloproliferative syndrome 2A22 Approved [5]
Systemic lupus erythematosus 4A40.0 Approved [4]
Systemic sclerosis 4A42 Approved [4]
Neuroblastoma 2D11.2 Investigative [4]
Retinoblastoma 2D02.2 Investigative [4]
Busulfan Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [25]
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Busulfan Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [26]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [27]
Glutathione S-transferase alpha-2 (GSTA2) DEH49YS GSTA2_HUMAN Metabolism [28]
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [29]
Microsomal glutathione S-transferase 2 (MGST2) DE31KMQ MGST2_HUMAN Metabolism [30]
Glutathione S-transferase mu-1 (GSTM1) DEYZEJA GSTM1_HUMAN Metabolism [29]
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⏷ Show the Full List of 6 DME(s)
Busulfan Interacts with 34 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Affects Abundance [31]
Glutathione S-transferase Mu 1 (GSTM1) OTSBF2MO GSTM1_HUMAN Affects Abundance [31]
Microsomal glutathione S-transferase 2 (MGST2) OT4UGTDO MGST2_HUMAN Decreases Response To Substance [30]
Glutathione S-transferase A1 (GSTA1) OTA7K5XA GSTA1_HUMAN Decreases Response To Substance [32]
Serotransferrin (TF) OT41PEMS TRFE_HUMAN Increases Expression [33]
Inhibin beta A chain (INHBA) OTSP64PQ INHBA_HUMAN Increases Expression [33]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [33]
Antithrombin-III (SERPINC1) OTDFATG0 ANT3_HUMAN Affects Expression [34]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [35]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [35]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [24]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [36]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [35]
Thrombospondin-1 (THBS1) OT0ECWK3 TSP1_HUMAN Increases Expression [35]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [37]
Tissue factor pathway inhibitor (TFPI) OTA0FX16 TFPI1_HUMAN Decreases Expression [35]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [37]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [24]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [24]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Activity [38]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Activity [38]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Expression [24]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Affects Expression [24]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [38]
Signal transducer and activator of transcription 1-alpha/beta (STAT1) OTLMBUZ6 STAT1_HUMAN Affects Expression [24]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [39]
Signal transducer and activator of transcription 2 (STAT2) OTO9G2RZ STAT2_HUMAN Decreases Expression [24]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [37]
Metal regulatory transcription factor 1 (MTF1) OTJWVLLF MTF1_HUMAN Decreases Expression [24]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [24]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [24]
Pseudouridylate synthase 7 homolog (PUS7) OTE5AQHJ PUS7_HUMAN Increases Expression [40]
DNA repair nuclease/redox regulator APEX1 (APEX1) OT53OI14 APEX1_HUMAN Increases Response To Substance [41]
Rho GDP-dissociation inhibitor 1 (ARHGDIA) OTEXWJDO GDIR1_HUMAN Affects Response To Substance [39]
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⏷ Show the Full List of 34 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult acute myeloid leukemia DCG8MX3 HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DCNV7MJ MOLT-4 Investigative [1]
Chronic myelogenous leukemia DCF0SNB K-562 Investigative [1]
Glioma DCML76U SF-539 Investigative [1]
Plasma cell myeloma DCRIJ1K RPMI-8226 Investigative [1]
Colon adenocarcinoma DCKJNFK COLO 205 Investigative [42]
High grade ovarian serous adenocarcinoma DC6MYBF OVCAR-4 Investigative [43]
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⏷ Show the Full List of 7 DrugCom(s)

References

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33 Busulfan induces activin A expression in vitro and in vivo: a possible link to venous occlusive disease. Clin Pharmacol Ther. 2003 Sep;74(3):264-74.
34 Decreased incidence of hepatic veno-occlusive disease and fewer hemostatic derangements associated with intravenous busulfan vs oral busulfan in adults conditioned with busulfan + cyclophosphamide for allogeneic bone marrow transplantation. Ann Hematol. 2005 May;84(5):321-30. doi: 10.1007/s00277-004-0982-4. Epub 2004 Dec 4.
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36 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
37 Altered gene expression in busulfan-resistant human myeloid leukemia. Leuk Res. 2008 Nov;32(11):1684-97. doi: 10.1016/j.leukres.2008.01.016. Epub 2008 Mar 12.
38 Busulfan selectively induces cellular senescence but not apoptosis in WI38 fibroblasts via a p53-independent but extracellular signal-regulated kinase-p38 mitogen-activated protein kinase-dependent mechanism. J Pharmacol Exp Ther. 2006 Nov;319(2):551-60. doi: 10.1124/jpet.106.107771. Epub 2006 Aug 1.
39 Reduced expression of Rho guanine nucleotide dissociation inhibitor-alpha modulates the cytotoxic effect of busulfan in HEK293 cells. Anticancer Drugs. 2007 Mar;18(3):333-40. doi: 10.1097/CAD.0b013e328011fd7f.
40 CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
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43 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.