Details of the Drug Combination

General Information of Drug Combination (ID: DC121B9)

Drug Combination Name
Dacarbazine Sorafenib
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Dacarbazine   DMNPZL4 Sorafenib   DMS8IFC
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HT29
Zero Interaction Potency (ZIP) Score: 0.35
Bliss Independence Score: 7.15
Loewe Additivity Score: 0.7
LHighest Single Agent (HSA) Score: 6.57

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Dacarbazine
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [2]
Astrocytoma 2A00.0Y Approved [2]
Brain disease 8C70-8E61 Approved [2]
Central nervous system disease 8A04-8D87 Approved [2]
Glioblastoma 2A00 Approved [2]
Gliosarcoma N.A. Approved [2]
Melanoma 2C30 Approved [3]
Classic Hodgkin lymphoma N.A. Investigative [2]
Neuroblastoma 2D11.2 Investigative [2]
Dacarbazine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Breaker [7]
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Dacarbazine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [9]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [10]
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Dacarbazine Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Increases Expression [11]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [6]
Interferon regulatory factor 1 (IRF1) OT43DI6J IRF1_HUMAN Increases Expression [12]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Decreases Activity [13]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Response To Substance [14]
DNA repair nuclease/redox regulator APEX1 (APEX1) OT53OI14 APEX1_HUMAN Increases Response To Substance [15]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) OTA675TJ GTR1_HUMAN Decreases Response To Substance [16]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Response To Substance [17]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Response To Substance [17]
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Affects Response To Substance [18]
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) OTS3FVTY M3K1_HUMAN Decreases Response To Substance [17]
Erythropoietin (EPO) OTZ90CN4 EPO_HUMAN Decreases Response To Substance [19]
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⏷ Show the Full List of 12 DOT(s)
Indication(s) of Sorafenib
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [4]
Carcinoma 2A00-2F9Z Approved [4]
Clear cell renal carcinoma N.A. Approved [4]
Lung cancer 2C25.0 Approved [4]
Medullary thyroid gland carcinoma N.A. Approved [4]
Non-small-cell lung cancer 2C25.Y Approved [4]
Renal cell carcinoma 2C90 Approved [5]
Thyroid cancer 2D10 Approved [4]
Hepatocellular carcinoma 2C12.02 Phase 3 [5]
Myelodysplastic syndrome 2A37 Phase 2 [5]
Sorafenib Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Modulator [25]
Platelet-derived growth factor receptor beta (PDGFRB) TTI7421 PGFRB_HUMAN Modulator [25]
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [26]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [25]
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Sorafenib Interacts with 7 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [27]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [28]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [29]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [30]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [31]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [30]
RalBP1-associated Eps domain-containing protein 2 (RALBP1) DTYEM9B REPS2_HUMAN Substrate [32]
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⏷ Show the Full List of 7 DTP(s)
Sorafenib Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [33]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [34]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [35]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [35]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [33]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [36]
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⏷ Show the Full List of 6 DME(s)
Sorafenib Interacts with 112 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Activity [37]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Affects Response To Substance [38]
Mast/stem cell growth factor receptor Kit (KIT) OTHUY3VZ KIT_HUMAN Decreases Phosphorylation [39]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [40]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [41]
DNA damage-inducible transcript 4 protein (DDIT4) OTHY8SY4 DDIT4_HUMAN Increases Expression [41]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [42]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Activity [43]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Activity [43]
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PIK3C2A) OTFBU4GD P3C2A_HUMAN Decreases Expression [20]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [20]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [20]
GTPase NRas (NRAS) OTVQ1DG3 RASN_HUMAN Decreases Expression [20]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Decreases Expression [20]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [20]
Protein kinase C alpha type (PRKCA) OT5UWNRD KPCA_HUMAN Decreases Expression [20]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Expression [20]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) OTTOMI8J PK3CA_HUMAN Decreases Expression [20]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Expression [20]
Cyclin-dependent kinase 9 (CDK9) OT2B7OGB CDK9_HUMAN Decreases Expression [20]
Growth factor receptor-bound protein 2 (GRB2) OTOP7LTE GRB2_HUMAN Decreases Expression [20]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Increases Expression [20]
Interferon regulatory factor 5 (IRF5) OT8SIIAP IRF5_HUMAN Increases Expression [20]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [20]
Serine/threonine-protein kinase PLK3 (PLK3) OT19CT2Z PLK3_HUMAN Increases Expression [20]
Serine/threonine-protein kinase PLK2 (PLK2) OTKMJXJ8 PLK2_HUMAN Increases Expression [20]
Histone deacetylase 6 (HDAC6) OT9W9MXQ HDAC6_HUMAN Decreases Expression [20]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [41]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [44]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Decreases Expression [45]
Zinc finger protein SNAI2 (SNAI2) OT7Y8EJ2 SNAI2_HUMAN Decreases Expression [21]
E3 ubiquitin-protein ligase parkin (PRKN) OTJBN41W PRKN_HUMAN Increases Ubiquitination [46]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [47]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) OTYG179K PR15A_HUMAN Increases Expression [22]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G) OT8V1J4M GA45G_HUMAN Increases Expression [48]
Apoptosis-inducing factor 1, mitochondrial (AIFM1) OTKPWB7Q AIFM1_HUMAN Affects Localization [45]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Activity [49]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Decreases Expression [50]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Activity [51]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Secretion [52]
RAF proto-oncogene serine/threonine-protein kinase (RAF1) OT51LSFO RAF1_HUMAN Decreases Activity [39]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [53]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [47]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Phosphorylation [54]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [55]
Eukaryotic translation initiation factor 4E (EIF4E) OTDAWNLA IF4E_HUMAN Decreases Phosphorylation [45]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) OTLU040A RET_HUMAN Decreases Activity [56]
High mobility group protein B1 (HMGB1) OT4B7CPF HMGB1_HUMAN Increases Expression [52]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [57]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Activity [49]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [37]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [58]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Increases Expression [21]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Activity [59]
Serine/threonine-protein kinase B-raf (BRAF) OT7S81XQ BRAF_HUMAN Decreases Activity [60]
Platelet-derived growth factor receptor alpha (PDGFRA) OTDJXUCN PGFRA_HUMAN Decreases Phosphorylation [61]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [41]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [62]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [63]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [64]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [64]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [58]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Expression [65]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Decreases Phosphorylation [39]
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2) OTUE7Z91 MP2K2_HUMAN Decreases Phosphorylation [60]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Phosphorylation [66]
Signal transducer and activator of transcription 5A (STAT5A) OTBSJGN3 STA5A_HUMAN Decreases Activity [67]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Expression [68]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Decreases Phosphorylation [50]
Mitogen-activated protein kinase 9 (MAPK9) OTCEVJ9E MK09_HUMAN Decreases Phosphorylation [50]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4) OTZPZX11 MP2K4_HUMAN Decreases Phosphorylation [50]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [49]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [69]
CCAAT/enhancer-binding protein delta (CEBPD) OTNBIPMY CEBPD_HUMAN Increases Expression [48]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [68]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10) OT4PXBTA TNF10_HUMAN Increases Response To Substance [70]
Stanniocalcin-1 (STC1) OTGVVXYF STC1_HUMAN Decreases Expression [71]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [72]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [54]
Gasdermin-D (GSDMD) OTH39BKI GSDMD_HUMAN Increases Expression [52]
Sestrin-2 (SESN2) OT889IXY SESN2_HUMAN Increases Expression [73]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [74]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [75]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [58]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Decreases Phosphorylation [60]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Cleavage [45]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [45]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [76]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [77]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [62]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [78]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Decreases Expression [79]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Cleavage [23]
Mitogen-activated protein kinase 14 (MAPK14) OT5TCO3O MK14_HUMAN Decreases Expression [80]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Decreases Expression [45]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [81]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [23]
Docking protein 1 (DOK1) OTGVRLW6 DOK1_HUMAN Decreases Phosphorylation [49]
Serine/threonine-protein kinase PINK1, mitochondrial (PINK1) OT50NR57 PINK1_HUMAN Increases Expression [46]
Eukaryotic translation initiation factor 2A (EIF2A) OTWXELQP EIF2A_HUMAN Increases Phosphorylation [22]
Autophagy protein 5 (ATG5) OT4T5SMS ATG5_HUMAN Increases Expression [82]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [83]
Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD) OT37FKH0 CYLD_HUMAN Increases Expression [40]
Diablo IAP-binding mitochondrial protein (DIABLO) OTHJ9MCZ DBLOH_HUMAN Affects Localization [79]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Phosphorylation [22]
E3 ubiquitin-protein ligase TRIM62 (TRIM62) OT15YO6N TRI62_HUMAN Affects Response To Substance [84]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Response To Substance [45]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Affects Response To Substance [38]
Hepatocyte growth factor (HGF) OTGHUA23 HGF_HUMAN Decreases Response To Substance [85]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Affects Response To Substance [38]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Increases Response To Substance [74]
Na(+)/citrate cotransporter (SLC13A5) OTPH1TA7 S13A5_HUMAN Decreases Response To Substance [86]
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⏷ Show the Full List of 112 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Anaplastic large cell lymphoma DC7KPL1 SR Investigative [1]
Cutaneous melanoma DCSFNPL SK-MEL-5 Investigative [1]
Glioma DC9K1DG SF-295 Investigative [1]
High grade ovarian serous adenocarcinoma DC43SEZ OVCAR-8 Investigative [1]
Lung adenocarcinoma DCPW4SU HOP-62 Investigative [1]
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35 Drug Interactions Flockhart Table
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55 Cell cycle dependent and schedule-dependent antitumor effects of sorafenib combined with radiation. Cancer Res. 2007 Oct 1;67(19):9443-54. doi: 10.1158/0008-5472.CAN-07-1473.
56 Sorafenib functions to potently suppress RET tyrosine kinase activity by direct enzymatic inhibition and promoting RET lysosomal degradation independent of proteasomal targeting. J Biol Chem. 2007 Oct 5;282(40):29230-40. doi: 10.1074/jbc.M703461200. Epub 2007 Jul 30.
57 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.
58 Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. J Pharmacol Exp Ther. 2006 Dec;319(3):1070-80. doi: 10.1124/jpet.106.108621. Epub 2006 Sep 7.
59 Sorafenib induces apoptosis in HL60 cells by inhibiting Src kinase-mediated STAT3 phosphorylation. Anticancer Drugs. 2011 Jan;22(1):79-88. doi: 10.1097/CAD.0b013e32833f44fd.
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71 Downregulation of stanniocalcin 1 is responsible for sorafenib-induced cardiotoxicity. Toxicol Sci. 2015 Feb;143(2):374-84. doi: 10.1093/toxsci/kfu235. Epub 2014 Nov 3.
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79 GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines. J Biol Chem. 2008 Jan 11;283(2):726-32. doi: 10.1074/jbc.M705343200. Epub 2007 Nov 8.
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