Details of the Drug Combination

General Information of Drug Combination (ID: DC7KPL1)

Drug Combination Name
Dacarbazine Sorafenib
Indication
Disease Entry Status REF
Anaplastic large cell lymphoma 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: SR
Zero Interaction Potency (ZIP) Score: 5.69
Bliss Independence Score: 5.23
Loewe Additivity Score: 5.82
LHighest Single Agent (HSA) Score: 7.86

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
Adenocarcinoma DC121B9 HT29 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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References

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35 Drug Interactions Flockhart Table
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42 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
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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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