Details of the Drug Combination

General Information of Drug Combination (ID: DCSGSZD)

Drug Combination Name
Ezetimibe Sorafenib
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Ezetimibe   DM7A8TW Sorafenib   DMS8IFC
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: 13.07
Bliss Independence Score: 13.07
Loewe Additivity Score: 24.61
LHighest Single Agent (HSA) Score: 24.62

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ezetimibe
Disease Entry ICD 11 Status REF
Atherosclerosis BD40 Approved [2]
Hypercholesterolaemia 5C80.0 Approved [3]
Hyperlipidemia 5C80.Z Approved [2]
Hyperlipidemia, familial combined, LPL related N.A. Approved [2]
Non-alcoholic fatty liver disease DB92 Approved [2]
Type-1/2 diabetes 5A10-5A11 Approved [2]
Ezetimibe Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Niemann-Pick C1-like protein 1 (NPC1L1) TTPD1CN NPCL1_HUMAN Inhibitor [7]
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Ezetimibe Interacts with 6 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [8]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [10]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [11]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [10]
Bile salt export pump (ABCB11) DTJ0EW4 ABCBB_HUMAN Substrate [12]
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⏷ Show the Full List of 6 DTP(s)
Ezetimibe Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [13]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [13]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [13]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [14]
UDP-glucuronosyltransferase 2B15 (UGT2B15) DENZ6B1 UDB15_HUMAN Metabolism [13]
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Ezetimibe Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [12]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases Activity [15]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Decreases Expression [16]
Retinoic acid receptor gamma (RARG) OT8LHMDH RARG_HUMAN Decreases Expression [16]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Decreases Expression [16]
Oxysterols receptor LXR-beta (NR1H2) OT4APA60 NR1H2_HUMAN Decreases Expression [16]
Sterol regulatory element-binding protein 2 (SREBF2) OTBXUNPL SRBP2_HUMAN Decreases Expression [16]
Scavenger receptor class B member 1 (SCARB1) OTAE1UA1 SCRB1_HUMAN Decreases Expression [16]
NPC1-like intracellular cholesterol transporter 1 (NPC1L1) OT6GWW1P NPCL1_HUMAN Decreases Response To Substance [17]
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⏷ Show the Full List of 9 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 [23]
Platelet-derived growth factor receptor beta (PDGFRB) TTI7421 PGFRB_HUMAN Modulator [23]
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [24]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [23]
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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 [25]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [26]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [27]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [28]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [29]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [28]
RalBP1-associated Eps domain-containing protein 2 (RALBP1) DTYEM9B REPS2_HUMAN Substrate [30]
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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 [31]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [32]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [33]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [33]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [31]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [34]
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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 [35]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Affects Response To Substance [36]
Mast/stem cell growth factor receptor Kit (KIT) OTHUY3VZ KIT_HUMAN Decreases Phosphorylation [37]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [38]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [39]
DNA damage-inducible transcript 4 protein (DDIT4) OTHY8SY4 DDIT4_HUMAN Increases Expression [39]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [40]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Activity [41]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Activity [41]
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PIK3C2A) OTFBU4GD P3C2A_HUMAN Decreases Expression [18]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [18]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [18]
GTPase NRas (NRAS) OTVQ1DG3 RASN_HUMAN Decreases Expression [18]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Decreases Expression [18]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [18]
Protein kinase C alpha type (PRKCA) OT5UWNRD KPCA_HUMAN Decreases Expression [18]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Expression [18]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) OTTOMI8J PK3CA_HUMAN Decreases Expression [18]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Expression [18]
Cyclin-dependent kinase 9 (CDK9) OT2B7OGB CDK9_HUMAN Decreases Expression [18]
Growth factor receptor-bound protein 2 (GRB2) OTOP7LTE GRB2_HUMAN Decreases Expression [18]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Increases Expression [18]
Interferon regulatory factor 5 (IRF5) OT8SIIAP IRF5_HUMAN Increases Expression [18]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [18]
Serine/threonine-protein kinase PLK3 (PLK3) OT19CT2Z PLK3_HUMAN Increases Expression [18]
Serine/threonine-protein kinase PLK2 (PLK2) OTKMJXJ8 PLK2_HUMAN Increases Expression [18]
Histone deacetylase 6 (HDAC6) OT9W9MXQ HDAC6_HUMAN Decreases Expression [18]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [39]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [42]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Decreases Expression [43]
Zinc finger protein SNAI2 (SNAI2) OT7Y8EJ2 SNAI2_HUMAN Decreases Expression [19]
E3 ubiquitin-protein ligase parkin (PRKN) OTJBN41W PRKN_HUMAN Increases Ubiquitination [44]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [45]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) OTYG179K PR15A_HUMAN Increases Expression [20]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G) OT8V1J4M GA45G_HUMAN Increases Expression [46]
Apoptosis-inducing factor 1, mitochondrial (AIFM1) OTKPWB7Q AIFM1_HUMAN Affects Localization [43]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Activity [47]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Decreases Expression [48]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Activity [49]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Secretion [50]
RAF proto-oncogene serine/threonine-protein kinase (RAF1) OT51LSFO RAF1_HUMAN Decreases Activity [37]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [51]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [45]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Phosphorylation [52]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [53]
Eukaryotic translation initiation factor 4E (EIF4E) OTDAWNLA IF4E_HUMAN Decreases Phosphorylation [43]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) OTLU040A RET_HUMAN Decreases Activity [54]
High mobility group protein B1 (HMGB1) OT4B7CPF HMGB1_HUMAN Increases Expression [50]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [55]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Activity [47]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [35]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [56]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Increases Expression [19]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Activity [57]
Serine/threonine-protein kinase B-raf (BRAF) OT7S81XQ BRAF_HUMAN Decreases Activity [58]
Platelet-derived growth factor receptor alpha (PDGFRA) OTDJXUCN PGFRA_HUMAN Decreases Phosphorylation [59]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [39]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [60]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [61]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [62]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [62]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [56]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Expression [63]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Decreases Phosphorylation [37]
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2) OTUE7Z91 MP2K2_HUMAN Decreases Phosphorylation [58]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Phosphorylation [64]
Signal transducer and activator of transcription 5A (STAT5A) OTBSJGN3 STA5A_HUMAN Decreases Activity [65]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Expression [66]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Decreases Phosphorylation [48]
Mitogen-activated protein kinase 9 (MAPK9) OTCEVJ9E MK09_HUMAN Decreases Phosphorylation [48]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4) OTZPZX11 MP2K4_HUMAN Decreases Phosphorylation [48]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [47]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [67]
CCAAT/enhancer-binding protein delta (CEBPD) OTNBIPMY CEBPD_HUMAN Increases Expression [46]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [66]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10) OT4PXBTA TNF10_HUMAN Increases Response To Substance [68]
Stanniocalcin-1 (STC1) OTGVVXYF STC1_HUMAN Decreases Expression [69]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [70]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [52]
Gasdermin-D (GSDMD) OTH39BKI GSDMD_HUMAN Increases Expression [50]
Sestrin-2 (SESN2) OT889IXY SESN2_HUMAN Increases Expression [71]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [72]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [73]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [56]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Decreases Phosphorylation [58]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Cleavage [43]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [43]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [74]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [75]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [60]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [76]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Decreases Expression [77]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Cleavage [21]
Mitogen-activated protein kinase 14 (MAPK14) OT5TCO3O MK14_HUMAN Decreases Expression [78]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Decreases Expression [43]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [79]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [21]
Docking protein 1 (DOK1) OTGVRLW6 DOK1_HUMAN Decreases Phosphorylation [47]
Serine/threonine-protein kinase PINK1, mitochondrial (PINK1) OT50NR57 PINK1_HUMAN Increases Expression [44]
Eukaryotic translation initiation factor 2A (EIF2A) OTWXELQP EIF2A_HUMAN Increases Phosphorylation [20]
Autophagy protein 5 (ATG5) OT4T5SMS ATG5_HUMAN Increases Expression [80]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [81]
Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD) OT37FKH0 CYLD_HUMAN Increases Expression [38]
Diablo IAP-binding mitochondrial protein (DIABLO) OTHJ9MCZ DBLOH_HUMAN Affects Localization [77]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Phosphorylation [20]
E3 ubiquitin-protein ligase TRIM62 (TRIM62) OT15YO6N TRI62_HUMAN Affects Response To Substance [82]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Response To Substance [43]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Affects Response To Substance [36]
Hepatocyte growth factor (HGF) OTGHUA23 HGF_HUMAN Decreases Response To Substance [83]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Affects Response To Substance [36]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Increases Response To Substance [72]
Na(+)/citrate cotransporter (SLC13A5) OTPH1TA7 S13A5_HUMAN Decreases Response To Substance [84]
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⏷ Show the Full List of 112 DOT(s)

References

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2 Ezetimibe FDA Label
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53 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.
54 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.
55 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.
56 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.
57 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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