General Information of Drug Combination (ID: DCP7QF6)

Drug Combination Name
Sorafenib Chlorambucil
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Sorafenib   DMS8IFC Chlorambucil   DMRKE63
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 22.52
Bliss Independence Score: 22.52
Loewe Additivity Score: 34.67
LHighest Single Agent (HSA) Score: 34.69

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Sorafenib
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [2]
Carcinoma 2A00-2F9Z Approved [2]
Clear cell renal carcinoma N.A. Approved [2]
Lung cancer 2C25.0 Approved [2]
Medullary thyroid gland carcinoma N.A. Approved [2]
Non-small-cell lung cancer 2C25.Y Approved [2]
Renal cell carcinoma 2C90 Approved [3]
Thyroid cancer 2D10 Approved [2]
Hepatocellular carcinoma 2C12.02 Phase 3 [3]
Myelodysplastic syndrome 2A37 Phase 2 [3]
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 [11]
Platelet-derived growth factor receptor beta (PDGFRB) TTI7421 PGFRB_HUMAN Modulator [11]
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [12]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [11]
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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 [13]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [14]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [15]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [16]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [17]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [16]
RalBP1-associated Eps domain-containing protein 2 (RALBP1) DTYEM9B REPS2_HUMAN Substrate [18]
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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 [19]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [20]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [21]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [21]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [19]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [22]
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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 [23]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Affects Response To Substance [24]
Mast/stem cell growth factor receptor Kit (KIT) OTHUY3VZ KIT_HUMAN Decreases Phosphorylation [25]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [26]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [27]
DNA damage-inducible transcript 4 protein (DDIT4) OTHY8SY4 DDIT4_HUMAN Increases Expression [27]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [28]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Activity [29]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Activity [29]
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PIK3C2A) OTFBU4GD P3C2A_HUMAN Decreases Expression [6]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [6]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [6]
GTPase NRas (NRAS) OTVQ1DG3 RASN_HUMAN Decreases Expression [6]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Decreases Expression [6]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [6]
Protein kinase C alpha type (PRKCA) OT5UWNRD KPCA_HUMAN Decreases Expression [6]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Expression [6]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) OTTOMI8J PK3CA_HUMAN Decreases Expression [6]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Expression [6]
Cyclin-dependent kinase 9 (CDK9) OT2B7OGB CDK9_HUMAN Decreases Expression [6]
Growth factor receptor-bound protein 2 (GRB2) OTOP7LTE GRB2_HUMAN Decreases Expression [6]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Increases Expression [6]
Interferon regulatory factor 5 (IRF5) OT8SIIAP IRF5_HUMAN Increases Expression [6]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [6]
Serine/threonine-protein kinase PLK3 (PLK3) OT19CT2Z PLK3_HUMAN Increases Expression [6]
Serine/threonine-protein kinase PLK2 (PLK2) OTKMJXJ8 PLK2_HUMAN Increases Expression [6]
Histone deacetylase 6 (HDAC6) OT9W9MXQ HDAC6_HUMAN Decreases Expression [6]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [27]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [30]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Decreases Expression [31]
Zinc finger protein SNAI2 (SNAI2) OT7Y8EJ2 SNAI2_HUMAN Decreases Expression [7]
E3 ubiquitin-protein ligase parkin (PRKN) OTJBN41W PRKN_HUMAN Increases Ubiquitination [32]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [33]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) OTYG179K PR15A_HUMAN Increases Expression [8]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G) OT8V1J4M GA45G_HUMAN Increases Expression [34]
Apoptosis-inducing factor 1, mitochondrial (AIFM1) OTKPWB7Q AIFM1_HUMAN Affects Localization [31]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Activity [35]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Decreases Expression [36]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Activity [37]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Secretion [38]
RAF proto-oncogene serine/threonine-protein kinase (RAF1) OT51LSFO RAF1_HUMAN Decreases Activity [25]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [39]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [33]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Phosphorylation [40]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [41]
Eukaryotic translation initiation factor 4E (EIF4E) OTDAWNLA IF4E_HUMAN Decreases Phosphorylation [31]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) OTLU040A RET_HUMAN Decreases Activity [42]
High mobility group protein B1 (HMGB1) OT4B7CPF HMGB1_HUMAN Increases Expression [38]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [43]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Activity [35]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [23]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [44]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Increases Expression [7]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Activity [45]
Serine/threonine-protein kinase B-raf (BRAF) OT7S81XQ BRAF_HUMAN Decreases Activity [46]
Platelet-derived growth factor receptor alpha (PDGFRA) OTDJXUCN PGFRA_HUMAN Decreases Phosphorylation [47]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [27]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [48]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [49]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [50]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [50]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [44]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Expression [51]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Decreases Phosphorylation [25]
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2) OTUE7Z91 MP2K2_HUMAN Decreases Phosphorylation [46]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Phosphorylation [52]
Signal transducer and activator of transcription 5A (STAT5A) OTBSJGN3 STA5A_HUMAN Decreases Activity [53]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Expression [54]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Decreases Phosphorylation [36]
Mitogen-activated protein kinase 9 (MAPK9) OTCEVJ9E MK09_HUMAN Decreases Phosphorylation [36]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4) OTZPZX11 MP2K4_HUMAN Decreases Phosphorylation [36]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [35]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [55]
CCAAT/enhancer-binding protein delta (CEBPD) OTNBIPMY CEBPD_HUMAN Increases Expression [34]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [54]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10) OT4PXBTA TNF10_HUMAN Increases Response To Substance [56]
Stanniocalcin-1 (STC1) OTGVVXYF STC1_HUMAN Decreases Expression [57]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [58]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [40]
Gasdermin-D (GSDMD) OTH39BKI GSDMD_HUMAN Increases Expression [38]
Sestrin-2 (SESN2) OT889IXY SESN2_HUMAN Increases Expression [59]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [60]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [61]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [44]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Decreases Phosphorylation [46]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Cleavage [31]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [31]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [62]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [63]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [48]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [64]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Decreases Expression [65]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Cleavage [9]
Mitogen-activated protein kinase 14 (MAPK14) OT5TCO3O MK14_HUMAN Decreases Expression [66]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Decreases Expression [31]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [67]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [9]
Docking protein 1 (DOK1) OTGVRLW6 DOK1_HUMAN Decreases Phosphorylation [35]
Serine/threonine-protein kinase PINK1, mitochondrial (PINK1) OT50NR57 PINK1_HUMAN Increases Expression [32]
Eukaryotic translation initiation factor 2A (EIF2A) OTWXELQP EIF2A_HUMAN Increases Phosphorylation [8]
Autophagy protein 5 (ATG5) OT4T5SMS ATG5_HUMAN Increases Expression [68]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [69]
Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD) OT37FKH0 CYLD_HUMAN Increases Expression [26]
Diablo IAP-binding mitochondrial protein (DIABLO) OTHJ9MCZ DBLOH_HUMAN Affects Localization [65]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Phosphorylation [8]
E3 ubiquitin-protein ligase TRIM62 (TRIM62) OT15YO6N TRI62_HUMAN Affects Response To Substance [70]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Response To Substance [31]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Affects Response To Substance [24]
Hepatocyte growth factor (HGF) OTGHUA23 HGF_HUMAN Decreases Response To Substance [71]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Affects Response To Substance [24]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Increases Response To Substance [60]
Na(+)/citrate cotransporter (SLC13A5) OTPH1TA7 S13A5_HUMAN Decreases Response To Substance [72]
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⏷ Show the Full List of 112 DOT(s)
Indication(s) of Chlorambucil
Disease Entry ICD 11 Status REF
Chronic lymphocytic leukaemia 2A82.0 Approved [4]
Small lymphocytic lymphoma 2A82.0 Approved [5]
Classic Hodgkin lymphoma N.A. Investigative [5]
Follicular lymphoma 2A80 Investigative [5]
Chlorambucil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA replication (DNA repli) TTABD5E NOUNIPROTAC Intercalator [73]
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Chlorambucil Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [74]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [75]
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Chlorambucil Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [76]
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Chlorambucil Interacts with 37 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Response To Substance [77]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [78]
Glutathione S-transferase A1 (GSTA1) OTA7K5XA GSTA1_HUMAN Decreases Activity [79]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Decreases Expression [80]
Leukemia inhibitory factor (LIF) OTO46S5S LIF_HUMAN Increases Expression [80]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Decreases Expression [80]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Expression [80]
F-box only protein 30 (FBXO30) OTD1P6LA FBX30_HUMAN Decreases Expression [80]
Histone chaperone ASF1A (ASF1A) OT4S44GP ASF1A_HUMAN Decreases Expression [80]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) OTBPCU2O TR10A_HUMAN Affects Expression [81]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [82]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Affects Expression [83]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Increases Expression [84]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [82]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [84]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [85]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1) OT7OG7Y2 DPA1_HUMAN Affects Expression [86]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [87]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Increases Expression [82]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [88]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [87]
Histone H4 (H4C1) OTB71W46 H4_HUMAN Decreases Expression [85]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Increases Expression [83]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Increases Expression [89]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [90]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [87]
kinase isozyme 4, mitochondrial (PDK4) OTCMHMBZ PDK4_HUMAN Affects Expression [91]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [83]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Response To Substance [92]
Dihydrofolate reductase (DHFR) OT3DVIGM DYR_HUMAN Decreases Response To Substance [93]
Cytidine deaminase (CDA) OT3HXP6N CDD_HUMAN Decreases Response To Substance [94]
Fanconi anemia group G protein (FANCG) OT7MC8TZ FANCG_HUMAN Increases Response To Substance [95]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [96]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Response To Substance [77]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Affects Export [97]
Glutathione S-transferase Mu 1 (GSTM1) OTSBF2MO GSTM1_HUMAN Decreases Response To Substance [98]
Fanconi anemia group C protein (FANCC) OTTIDM3P FANCC_HUMAN Increases Response To Substance [95]
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⏷ Show the Full List of 37 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Clear cell renal cell carcinoma DCIHDZV A498 Investigative [1]
Lung adenocarcinoma DCFX6AO HOP-62 Investigative [1]
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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 Sorafenib FDA Label
3 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: 5711).
4 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: 7143).
5 Chlorambucil FDA Label
6 Novel carbocyclic curcumin analog CUR3d modulates genes involved in multiple apoptosis pathways in human hepatocellular carcinoma cells. Chem Biol Interact. 2015 Dec 5;242:107-22.
7 Destruxin B inhibits hepatocellular carcinoma cell growth through modulation of the Wnt/-catenin signaling pathway and epithelial-mesenchymal transition. Toxicol In Vitro. 2014 Jun;28(4):552-61. doi: 10.1016/j.tiv.2014.01.002. Epub 2014 Jan 13.
8 The kinase inhibitor sorafenib induces cell death through a process involving induction of endoplasmic reticulum stress. Mol Cell Biol. 2007 Aug;27(15):5499-513. doi: 10.1128/MCB.01080-06. Epub 2007 Jun 4.
9 Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway. Leukemia. 2008 Apr;22(4):808-18. doi: 10.1038/sj.leu.2405098. Epub 2008 Jan 17.
10 Ovatodiolide suppresses yes-associated protein 1-modulated cancer stem cell phenotypes in highly malignant hepatocellular carcinoma and sensitizes cancer cells to chemotherapy in vitro. Toxicol In Vitro. 2018 Sep;51:74-82. doi: 10.1016/j.tiv.2018.04.010. Epub 2018 Apr 24.
11 Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
12 Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
13 Multidrug resistance protein 2 implicates anticancer drug-resistance to sorafenib. Biol Pharm Bull. 2011;34(3):433-5.
14 Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation. Mol Cancer Ther. 2010 Feb;9(2):319-26.
15 Double-transduced MDCKII cells to study human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) interplay in drug transport across the blood-brain barrier. Mol Pharm. 2011 Apr 4;8(2):571-82.
16 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
17 Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma
18 Rlip76 transports sunitinib and sorafenib and mediates drug resistance in kidney cancer. Int J Cancer. 2010 Mar 15;126(6):1327-38.
19 Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
20 Ontogeny and sorafenib metabolism. Clin Cancer Res. 2012 Oct 15;18(20):5788-95.
21 Drug Interactions Flockhart Table
22 Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4.
23 Differential inhibition of human CYP2C8 and molecular docking interactions elicited by sorafenib and its major N-oxide metabolite. Chem Biol Interact. 2021 Apr 1;338:109401. doi: 10.1016/j.cbi.2021.109401. Epub 2021 Feb 5.
24 The Enhanced metastatic potential of hepatocellular carcinoma (HCC) cells with sorafenib resistance. PLoS One. 2013 Nov 11;8(11):e78675. doi: 10.1371/journal.pone.0078675. eCollection 2013.
25 Sorafenib induces growth suppression in mouse models of gastrointestinal stromal tumor. Mol Cancer Ther. 2009 Jan;8(1):152-9. doi: 10.1158/1535-7163.MCT-08-0553.
26 Down-regulation of CYLD as a trigger for NF-B activation and a mechanism of apoptotic resistance in hepatocellular carcinoma cells. Int J Oncol. 2011 Jan;38(1):121-31.
27 Sorafenib induces apoptotic cell death in human non-small cell lung cancer cells by down-regulating mammalian target of rapamycin (mTOR)-dependent survivin expression. Biochem Pharmacol. 2011 Aug 1;82(3):216-26. doi: 10.1016/j.bcp.2011.04.011. Epub 2011 May 13.
28 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.
29 Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines. BMC Cancer. 2012 Sep 10;12:402.
30 The multikinase inhibitor sorafenib potentiates TRAIL lethality in human leukemia cells in association with Mcl-1 and cFLIPL down-regulation. Cancer Res. 2007 Oct 1;67(19):9490-500. doi: 10.1158/0008-5472.CAN-07-0598.
31 Apoptosis induced by the kinase inhibitor BAY 43-9006 in human leukemia cells involves down-regulation of Mcl-1 through inhibition of translation. J Biol Chem. 2005 Oct 21;280(42):35217-27. doi: 10.1074/jbc.M506551200. Epub 2005 Aug 18.
32 Sorafenib targets the mitochondrial electron transport chain complexes and ATP synthase to activate the PINK1-Parkin pathway and modulate cellular drug response. J Biol Chem. 2017 Sep 8;292(36):15105-15120. doi: 10.1074/jbc.M117.783175. Epub 2017 Jul 3.
33 Induction of DNA damage-inducible gene GADD45beta contributes to sorafenib-induced apoptosis in hepatocellular carcinoma cells. Cancer Res. 2010 Nov 15;70(22):9309-18. doi: 10.1158/0008-5472.CAN-10-1033. Epub 2010 Nov 9.
34 Growth arrest DNA damage-inducible gene 45 gamma expression as a prognostic and predictive biomarker in hepatocellular carcinoma. Oncotarget. 2015 Sep 29;6(29):27953-65. doi: 10.18632/oncotarget.4446.
35 Sorafenib induces apoptosis specifically in cells expressing BCR/ABL by inhibiting its kinase activity to activate the intrinsic mitochondrial pathway. Cancer Res. 2009 May 1;69(9):3927-36. doi: 10.1158/0008-5472.CAN-08-2978. Epub 2009 Apr 14.
36 Synergistic antimetastatic effect of cotreatment with licochalcone A and sorafenib on human hepatocellular carcinoma cells through the inactivation of MKK4/JNK and uPA expression. Environ Toxicol. 2018 Dec;33(12):1237-1244. doi: 10.1002/tox.22630. Epub 2018 Sep 6.
37 Sorafenib inhibits transforming growth factor 1-mediated epithelial-mesenchymal transition and apoptosis in mouse hepatocytes. Hepatology. 2011 May;53(5):1708-18. doi: 10.1002/hep.24254.
38 Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events. Toxicol In Vitro. 2021 Mar;71:105063. doi: 10.1016/j.tiv.2020.105063. Epub 2020 Dec 1.
39 Sorafenib is an antagonist of the aryl hydrocarbon receptor. Toxicology. 2022 Mar 30;470:153118. doi: 10.1016/j.tox.2022.153118. Epub 2022 Feb 3.
40 Sorafenib induces cell death in chronic lymphocytic leukemia by translational downregulation of Mcl-1. Leukemia. 2011 May;25(5):838-47. doi: 10.1038/leu.2011.2. Epub 2011 Feb 4.
41 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.
42 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.
43 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.
44 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.
45 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.
46 Rap1/B-Raf signaling is activated in neuroendocrine tumors of the digestive tract and Raf kinase inhibition constitutes a putative therapeutic target. Neuroendocrinology. 2007;85(1):45-53. doi: 10.1159/000100508. Epub 2007 Mar 5.
47 Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies. Mol Cancer Ther. 2011 Jun;10(6):1028-35. doi: 10.1158/1535-7163.MCT-10-1044. Epub 2011 Apr 11.
48 Inhibition of autophagy potentiates the antitumor effect of the multikinase inhibitor sorafenib in hepatocellular carcinoma. Int J Cancer. 2012 Aug 1;131(3):548-57. doi: 10.1002/ijc.26374. Epub 2011 Sep 12.
49 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
50 Sorafenib inhibits signal transducer and activator of transcription 3 signaling associated with growth arrest and apoptosis of medulloblastomas. Mol Cancer Ther. 2008 Nov;7(11):3519-26. doi: 10.1158/1535-7163.MCT-08-0138.
51 Therapeutic targeting of hepatocellular carcinoma cells with antrocinol, a novel, dual-specificity, small-molecule inhibitor of the KRAS and ERK oncogenic signaling pathways. Chem Biol Interact. 2023 Jan 25;370:110329. doi: 10.1016/j.cbi.2022.110329. Epub 2022 Dec 22.
52 Sorafenib derivatives induce apoptosis through inhibition of STAT3 independent of Raf. Eur J Med Chem. 2011 Jul;46(7):2845-51. doi: 10.1016/j.ejmech.2011.04.007. Epub 2011 Apr 14.
53 The multikinase inhibitor sorafenib induces apoptosis in highly imatinib mesylate-resistant bcr/abl+ human leukemia cells in association with signal transducer and activator of transcription 5 inhibition and myeloid cell leukemia-1 down-regulation. Mol Pharmacol. 2007 Sep;72(3):788-95. doi: 10.1124/mol.106.033308. Epub 2007 Jun 26.
54 Arsenic trioxide potentiates the anti-cancer activities of sorafenib against hepatocellular carcinoma by inhibiting Akt activation. Tumour Biol. 2015 Apr;36(4):2323-34. doi: 10.1007/s13277-014-2839-3. Epub 2014 Nov 22.
55 Proliferation and survival molecules implicated in the inhibition of BRAF pathway in thyroid cancer cells harbouring different genetic mutations. BMC Cancer. 2009 Oct 31;9:387. doi: 10.1186/1471-2407-9-387.
56 The multikinase inhibitor Sorafenib induces apoptosis and sensitises endometrial cancer cells to TRAIL by different mechanisms. Eur J Cancer. 2010 Mar;46(4):836-50. doi: 10.1016/j.ejca.2009.12.025. Epub 2010 Jan 12.
57 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.
58 Sorafenib induces preferential apoptotic killing of a drug- and radio-resistant Hep G2 cells through a mitochondria-dependent oxidative stress mechanism. Cancer Biol Ther. 2009 Oct;8(20):1904-13. doi: 10.4161/cbt.8.20.9436. Epub 2009 Oct 6.
59 Protective effect of sestrin2 against iron overload and ferroptosis-induced liver injury. Toxicol Appl Pharmacol. 2019 Sep 15;379:114665. doi: 10.1016/j.taap.2019.114665. Epub 2019 Jul 16.
60 Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment. Cancer Lett. 2013 Feb 1;329(1):45-58. doi: 10.1016/j.canlet.2012.09.020. Epub 2012 Oct 2.
61 The role of Mcl-1 downregulation in the proapoptotic activity of the multikinase inhibitor BAY 43-9006. Oncogene. 2005 Oct 20;24(46):6861-9. doi: 10.1038/sj.onc.1208841.
62 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.
63 The multikinase inhibitor sorafenib induces caspase-dependent apoptosis in PC-3 prostate cancer cells. Asian J Androl. 2010 Jul;12(4):527-34. doi: 10.1038/aja.2010.21. Epub 2010 May 17.
64 Synergistic inhibition of human melanoma proliferation by combination treatment with B-Raf inhibitor BAY43-9006 and mTOR inhibitor Rapamycin. J Transl Med. 2005 Oct 28;3:39. doi: 10.1186/1479-5876-3-39.
65 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.
66 Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways. Mol Cancer Ther. 2006 Sep;5(9):2378-87. doi: 10.1158/1535-7163.MCT-06-0235.
67 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.
68 Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation. Cancer Biol Ther. 2008 Oct;7(10):1648-62. doi: 10.4161/cbt.7.10.6623. Epub 2008 Oct 12.
69 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.
70 TRIM62 silencing represses the proliferation and invasion and increases the chemosensitivity of hepatocellular carcinoma cells by affecting the NF-B pathway. Toxicol Appl Pharmacol. 2022 Jun 15;445:116035. doi: 10.1016/j.taap.2022.116035. Epub 2022 Apr 23.
71 Diospyros kaki leaves inhibit HGF/Met signaling-mediated EMT and stemness features in hepatocellular carcinoma. Food Chem Toxicol. 2020 Aug;142:111475. doi: 10.1016/j.fct.2020.111475. Epub 2020 Jun 6.
72 Comparative proteomic analysis of SLC13A5 knockdown reveals elevated ketogenesis and enhanced cellular toxic response to chemotherapeutic agents in HepG2 cells. Toxicol Appl Pharmacol. 2020 Sep 1;402:115117. doi: 10.1016/j.taap.2020.115117. Epub 2020 Jul 4.
73 Roles of DNA repair and reductase activity in the cytotoxicity of the hypoxia-activated dinitrobenzamide mustard PR-104A. Mol Cancer Ther. 2009 Jun;8(6):1714-23.
74 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
75 Transporters and renal drug elimination. Annu Rev Pharmacol Toxicol. 2004;44:137-66.
76 The anti-cancer drug chlorambucil as a substrate for the human polymorphic enzyme glutathione transferase P1-1: kinetic properties and crystallographic characterisation of allelic variants. J Mol Biol. 2008 Jun 27;380(1):131-44.
77 The influence of coordinate overexpression of glutathione phase II detoxification gene products on drug resistance. J Pharmacol Exp Ther. 2000 Aug;294(2):480-7.
78 Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs. Int J Cancer. 2004 Sep 10;111(4):484-93. doi: 10.1002/ijc.20230.
79 Role of multidrug resistance protein 1 (MRP1) and glutathione S-transferase A1-1 in alkylating agent resistanceKinetics of glutathione conjugate formation and efflux govern differential cellular sensitivity to chlorambucil versus melphalan toxicity. J Biol Chem. 2001 Mar 16;276(11):7952-6.
80 Oxidative stress mechanisms do not discriminate between genotoxic and nongenotoxic liver carcinogens. Chem Res Toxicol. 2015 Aug 17;28(8):1636-46.
81 Role of the TRAIL/APO2-L death receptors in chlorambucil- and fludarabine-induced apoptosis in chronic lymphocytic leukemia. Oncogene. 2003 Nov 13;22(51):8356-69. doi: 10.1038/sj.onc.1207004.
82 Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells. J Cell Biochem. 2008 May 15;104(2):595-605. doi: 10.1002/jcb.21649.
83 Differential gene expression induction by TRAIL in B chronic lymphocytic leukemia (B-CLL) cells showing high versus low levels of Zap-70. J Cell Physiol. 2007 Oct;213(1):229-36. doi: 10.1002/jcp.21116.
84 Theophylline synergizes with chlorambucil in inducing apoptosis of B-chronic lymphocytic leukemia cells. Blood. 1996 Sep 15;88(6):2172-82.
85 A two-hit mechanism for pre-mitotic arrest of cancer cell proliferation by a polyamide-alkylator conjugate. Cell Cycle. 2006 Jul;5(14):1537-48. doi: 10.4161/cc.5.14.2913. Epub 2006 Jul 17.
86 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
87 Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation. Blood. 2001 Nov 1;98(9):2800-7. doi: 10.1182/blood.v98.9.2800.
88 Disruption of gene expression and induction of apoptosis in prostate cancer cells by a DNA-damaging agent tethered to an androgen receptor ligand. Chem Biol. 2005 Jul;12(7):779-87. doi: 10.1016/j.chembiol.2005.05.009.
89 Chlorambucil induction of HsRad51 in B-cell chronic lymphocytic leukemia. Clin Cancer Res. 1999 Aug;5(8):2178-84.
90 Bcl-2 antisense oligonucleotides enhance the cytotoxicity of chlorambucil in B-cell chronic lymphocytic leukaemia cells. Leuk Lymphoma. 2001 Jul;42(3):491-8. doi: 10.3109/10428190109064606.
91 The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. Neurotox Res. 2020 Dec;38(4):967-978. doi: 10.1007/s12640-020-00272-3. Epub 2020 Sep 1.
92 Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds. Carcinogenesis. 2009 Sep;30(9):1571-80. doi: 10.1093/carcin/bgp176. Epub 2009 Jul 16.
93 Increased resistance to nitrogen mustards and antifolates following in vitro selection of murine fibroblasts and primary hematopoietic cells transduced with a bicistronic retroviral vector expressing the rat glutathione S-transferase A3 and a mutant dihydrofolate reductase. Cancer Gene Ther. 2003 Aug;10(8):637-46. doi: 10.1038/sj.cgt.7700619.
94 Coexpression of rat glutathione S-transferase A3 and human cytidine deaminase by a bicistronic retroviral vector confers in vitro resistance to nitrogen mustards and cytosine arabinoside in murine fibroblasts. Cancer Gene Ther. 2000 May;7(5):757-65. doi: 10.1038/sj.cgt.7700169.
95 In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin Cancer Res. 2005 Oct 15;11(20):7508-15. doi: 10.1158/1078-0432.CCR-05-1048.
96 Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
97 Role of multidrug resistance protein 2 (MRP2, ABCC2) in alkylating agent detoxification: MRP2 potentiates glutathione S-transferase A1-1-mediated resistance to chlorambucil cytotoxicity. J Pharmacol Exp Ther. 2004 Jan;308(1):260-7. doi: 10.1124/jpet.103.057729. Epub 2003 Oct 20.
98 Glutathione S-transferase M1 and multidrug resistance protein 1 act in synergy to protect melanoma cells from vincristine effects. Mol Pharmacol. 2004 Apr;65(4):897-905. doi: 10.1124/mol.65.4.897.