General Information of Drug Combination (ID: DCQIOTJ)

Drug Combination Name
Dactinomycin Sorafenib
Indication
Disease Entry Status REF
High grade ovarian serous adenocarcinoma Investigative [1]
Component Drugs Dactinomycin   DM2YGNW Sorafenib   DMS8IFC
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: OVCAR-8
Zero Interaction Potency (ZIP) Score: 12.56
Bliss Independence Score: 10.85
Loewe Additivity Score: 10.07
LHighest Single Agent (HSA) Score: 9.49

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Dactinomycin
Disease Entry ICD 11 Status REF
Adult kidney Wilms tumor N.A. Approved [2]
Advanced cancer 2A00-2F9Z Approved [2]
Beckwith-Wiedemann syndrome N.A. Approved [2]
Childhood kidney Wilms tumor N.A. Approved [2]
Gestational trophoblastic neoplasia 2F33-2F76 Approved [2]
Hamartoma N.A. Approved [2]
Solid tumour/cancer 2A00-2F9Z Approved [3]
Wilms tumor N.A. Approved [2]
Dactinomycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Breaker [9]
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Dactinomycin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [10]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [12]
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Dactinomycin Interacts with 85 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Response To Substance [13]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Response To Substance [14]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Increases Expression [6]
Dihydropyrimidinase-related protein 4 (DPYSL4) OT3SBS2S DPYL4_HUMAN Increases Expression [6]
Integral membrane protein GPR137B (GPR137B) OT1CINQQ G137B_HUMAN Increases Expression [6]
Integrin alpha-IIb (ITGA2B) OT4Y17PY ITA2B_HUMAN Increases Expression [6]
Ras-related protein R-Ras (RRAS) OTBBF28C RRAS_HUMAN Increases Expression [6]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [6]
Stomatin (STOM) OTC8R6EH STOM_HUMAN Increases Expression [6]
Cellular retinoic acid-binding protein 2 (CRABP2) OTY01V9G RABP2_HUMAN Increases Expression [6]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Increases Expression [6]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Increases Expression [6]
Tumor necrosis factor ligand superfamily member 9 (TNFSF9) OTV9L89D TNFL9_HUMAN Increases Expression [6]
Galectin-7 (LGALS7) OTMSVI7R LEG7_HUMAN Increases Expression [6]
Large ribosomal subunit protein eL34 (RPL34) OT0U9VMQ RL34_HUMAN Increases Expression [6]
Rho GDP-dissociation inhibitor 2 (ARHGDIB) OT9PD6CS GDIR2_HUMAN Increases Expression [6]
Epithelial membrane protein 1 (EMP1) OTSZHUHQ EMP1_HUMAN Increases Expression [6]
Epithelial membrane protein 3 (EMP3) OTODMJ1D EMP3_HUMAN Increases Expression [6]
Protein ripply3 (RIPPLY3) OT1HK35I DSCR6_HUMAN Increases Expression [6]
Endonuclease III-like protein 1 (NTHL1) OTPQXPT1 NTH_HUMAN Decreases Expression [6]
Antigen peptide transporter 1 (TAP1) OTJL27PW TAP1_HUMAN Increases Expression [6]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [6]
Kinesin-like protein KIF1A (KIF1A) OT3JVEGV KIF1A_HUMAN Increases Expression [6]
Protein AF1q (MLLT11) OTG5RVHC AF1Q_HUMAN Increases Expression [6]
Laminin subunit gamma-2 (LAMC2) OTJMTM72 LAMC2_HUMAN Increases Expression [6]
Filamin-C (FLNC) OT3F8J6Y FLNC_HUMAN Increases Expression [6]
Immediate early response gene 5 protein (IER5) OTJPTXMD IER5_HUMAN Increases Expression [6]
Keratin, type II cytoskeletal 80 (KRT80) OTAU54U3 K2C80_HUMAN Increases Expression [6]
All-trans-retinol 13,14-reductase (RETSAT) OTC3AOPX RETST_HUMAN Increases Expression [6]
Interleukin-27 receptor subunit alpha (IL27RA) OTSQBAKI I27RA_HUMAN Increases Expression [6]
Neuropilin and tolloid-like protein 2 (NETO2) OT0YAMC0 NETO2_HUMAN Increases Expression [6]
Mitochondria-eating protein (SPATA18) OTOEHTHU MIEAP_HUMAN Increases Expression [6]
Phospholipase ABHD3 (ABHD3) OTH8P977 ABHD3_HUMAN Increases Expression [6]
Homer protein homolog 3 (HOMER3) OTQ6D9X1 HOME3_HUMAN Increases Expression [6]
BSD domain-containing protein 1 (BSDC1) OT853CP9 BSDC1_HUMAN Increases Expression [6]
Stathmin-3 (STMN3) OT20F289 STMN3_HUMAN Increases Expression [6]
Endothelial protein C receptor (PROCR) OTRHED17 EPCR_HUMAN Increases Expression [6]
Fatty acid desaturase 3 (FADS3) OT9RVXGE FADS3_HUMAN Increases Expression [6]
Protein O-mannosyl-transferase 1 (POMT1) OTGQSHL5 POMT1_HUMAN Increases Expression [6]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [15]
Tumor protein p53-inducible protein 11 (TP53I11) OTFPDYZU P5I11_HUMAN Decreases Expression [16]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Decreases Expression [17]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [18]
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7) OTUXEASC M3K7_HUMAN Decreases Expression [19]
Prominin-1 (PROM1) OTBHV8NX PROM1_HUMAN Decreases Expression [20]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [19]
Low-density lipoprotein receptor (LDLR) OTH559LU LDLR_HUMAN Decreases Expression [21]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Response To Substance [22]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Decreases Expression [23]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) OTBPMIMW G3P_HUMAN Increases Expression [19]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [24]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [25]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [23]
Proto-oncogene tyrosine-protein kinase ROS (ROS1) OTDSKUGE ROS1_HUMAN Increases Expression [19]
Fibroblast growth factor 2 (FGF2) OT7YUJ9F FGF2_HUMAN Decreases Expression [26]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Decreases Expression [27]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [28]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [29]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Decreases Expression [30]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [31]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [20]
CCAAT/enhancer-binding protein beta (CEBPB) OTM9MQIA CEBPB_HUMAN Decreases Expression [19]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Decreases Expression [19]
Lamin-B1 (LMNB1) OT100T3P LMNB1_HUMAN Decreases Expression [19]
rRNA 2'-O-methyltransferase fibrillarin (FBL) OTRODIE5 FBRL_HUMAN Affects Localization [32]
DNA-directed RNA polymerase II subunit RPB1 (POLR2A) OTHJQ1DZ RPB1_HUMAN Decreases Phosphorylation [33]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [34]
Signal transducer and activator of transcription 1-alpha/beta (STAT1) OTLMBUZ6 STAT1_HUMAN Increases Expression [19]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Expression [19]
Caspase-2 (CASP2) OTUDYSPP CASP2_HUMAN Increases Cleavage [35]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4) OTZPZX11 MP2K4_HUMAN Decreases Expression [19]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Decreases Expression [19]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Decreases Expression [36]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [37]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [38]
Son of sevenless homolog 1 (SOS1) OTTCWXC3 SOS1_HUMAN Decreases Expression [19]
FAS-associated death domain protein (FADD) OTV7GFHH FADD_HUMAN Decreases Expression [19]
Growth arrest-specific protein 6 (GAS6) OTPOPUUE GAS6_HUMAN Increases Degradation [39]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Decreases Expression [19]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [29]
Proheparin-binding EGF-like growth factor (HBEGF) OTLU00JS HBEGF_HUMAN Decreases Expression [26]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [40]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Decreases Expression [20]
Hyaluronidase-1 (HYAL1) OT2SJN0X HYAL1_HUMAN Increases ADR [41]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP) OTPYQX3K C1QBP_HUMAN Decreases Response To Substance [42]
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⏷ Show the Full List of 85 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 [48]
Platelet-derived growth factor receptor beta (PDGFRB) TTI7421 PGFRB_HUMAN Modulator [48]
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [49]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [48]
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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 [50]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [51]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [52]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [53]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [54]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [53]
RalBP1-associated Eps domain-containing protein 2 (RALBP1) DTYEM9B REPS2_HUMAN Substrate [55]
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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 [56]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [57]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [58]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [58]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [56]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [59]
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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 [60]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Affects Response To Substance [61]
Mast/stem cell growth factor receptor Kit (KIT) OTHUY3VZ KIT_HUMAN Decreases Phosphorylation [62]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [63]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [64]
DNA damage-inducible transcript 4 protein (DDIT4) OTHY8SY4 DDIT4_HUMAN Increases Expression [64]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [65]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Activity [66]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Activity [66]
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PIK3C2A) OTFBU4GD P3C2A_HUMAN Decreases Expression [43]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [43]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [43]
GTPase NRas (NRAS) OTVQ1DG3 RASN_HUMAN Decreases Expression [43]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Decreases Expression [43]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [43]
Protein kinase C alpha type (PRKCA) OT5UWNRD KPCA_HUMAN Decreases Expression [43]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Expression [43]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) OTTOMI8J PK3CA_HUMAN Decreases Expression [43]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Expression [43]
Cyclin-dependent kinase 9 (CDK9) OT2B7OGB CDK9_HUMAN Decreases Expression [43]
Growth factor receptor-bound protein 2 (GRB2) OTOP7LTE GRB2_HUMAN Decreases Expression [43]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Increases Expression [43]
Interferon regulatory factor 5 (IRF5) OT8SIIAP IRF5_HUMAN Increases Expression [43]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [43]
Serine/threonine-protein kinase PLK3 (PLK3) OT19CT2Z PLK3_HUMAN Increases Expression [43]
Serine/threonine-protein kinase PLK2 (PLK2) OTKMJXJ8 PLK2_HUMAN Increases Expression [43]
Histone deacetylase 6 (HDAC6) OT9W9MXQ HDAC6_HUMAN Decreases Expression [43]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [64]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [67]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Decreases Expression [68]
Zinc finger protein SNAI2 (SNAI2) OT7Y8EJ2 SNAI2_HUMAN Decreases Expression [44]
E3 ubiquitin-protein ligase parkin (PRKN) OTJBN41W PRKN_HUMAN Increases Ubiquitination [69]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [70]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) OTYG179K PR15A_HUMAN Increases Expression [45]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G) OT8V1J4M GA45G_HUMAN Increases Expression [71]
Apoptosis-inducing factor 1, mitochondrial (AIFM1) OTKPWB7Q AIFM1_HUMAN Affects Localization [68]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Activity [72]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Decreases Expression [73]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Activity [74]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Secretion [75]
RAF proto-oncogene serine/threonine-protein kinase (RAF1) OT51LSFO RAF1_HUMAN Decreases Activity [62]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [76]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [70]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Phosphorylation [77]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [78]
Eukaryotic translation initiation factor 4E (EIF4E) OTDAWNLA IF4E_HUMAN Decreases Phosphorylation [68]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) OTLU040A RET_HUMAN Decreases Activity [79]
High mobility group protein B1 (HMGB1) OT4B7CPF HMGB1_HUMAN Increases Expression [75]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [80]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Activity [72]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [60]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [81]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Increases Expression [44]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Activity [82]
Serine/threonine-protein kinase B-raf (BRAF) OT7S81XQ BRAF_HUMAN Decreases Activity [83]
Platelet-derived growth factor receptor alpha (PDGFRA) OTDJXUCN PGFRA_HUMAN Decreases Phosphorylation [84]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [64]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [85]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [86]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [87]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [87]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [81]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Expression [88]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Decreases Phosphorylation [62]
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2) OTUE7Z91 MP2K2_HUMAN Decreases Phosphorylation [83]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Phosphorylation [89]
Signal transducer and activator of transcription 5A (STAT5A) OTBSJGN3 STA5A_HUMAN Decreases Activity [90]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Expression [91]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Decreases Phosphorylation [73]
Mitogen-activated protein kinase 9 (MAPK9) OTCEVJ9E MK09_HUMAN Decreases Phosphorylation [73]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4) OTZPZX11 MP2K4_HUMAN Decreases Phosphorylation [73]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [72]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [92]
CCAAT/enhancer-binding protein delta (CEBPD) OTNBIPMY CEBPD_HUMAN Increases Expression [71]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [91]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10) OT4PXBTA TNF10_HUMAN Increases Response To Substance [93]
Stanniocalcin-1 (STC1) OTGVVXYF STC1_HUMAN Decreases Expression [94]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [95]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [77]
Gasdermin-D (GSDMD) OTH39BKI GSDMD_HUMAN Increases Expression [75]
Sestrin-2 (SESN2) OT889IXY SESN2_HUMAN Increases Expression [96]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [97]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [98]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [81]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Decreases Phosphorylation [83]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Cleavage [68]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [68]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [99]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [100]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [85]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [101]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Decreases Expression [102]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Cleavage [46]
Mitogen-activated protein kinase 14 (MAPK14) OT5TCO3O MK14_HUMAN Decreases Expression [103]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Decreases Expression [68]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [104]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [46]
Docking protein 1 (DOK1) OTGVRLW6 DOK1_HUMAN Decreases Phosphorylation [72]
Serine/threonine-protein kinase PINK1, mitochondrial (PINK1) OT50NR57 PINK1_HUMAN Increases Expression [69]
Eukaryotic translation initiation factor 2A (EIF2A) OTWXELQP EIF2A_HUMAN Increases Phosphorylation [45]
Autophagy protein 5 (ATG5) OT4T5SMS ATG5_HUMAN Increases Expression [105]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [40]
Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD) OT37FKH0 CYLD_HUMAN Increases Expression [63]
Diablo IAP-binding mitochondrial protein (DIABLO) OTHJ9MCZ DBLOH_HUMAN Affects Localization [102]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Phosphorylation [45]
E3 ubiquitin-protein ligase TRIM62 (TRIM62) OT15YO6N TRI62_HUMAN Affects Response To Substance [106]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Response To Substance [68]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Affects Response To Substance [61]
Hepatocyte growth factor (HGF) OTGHUA23 HGF_HUMAN Decreases Response To Substance [107]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Affects Response To Substance [61]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Increases Response To Substance [97]
Na(+)/citrate cotransporter (SLC13A5) OTPH1TA7 S13A5_HUMAN Decreases Response To Substance [108]
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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
Cutaneous melanoma DCT1JEK SK-MEL-28 Investigative [1]
Lung adenocarcinoma DC9XNQP MDA-MB-231 Investigative [1]
Melanoma DCP5V6I UACC-257 Investigative [1]
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References

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2 Dactinomycin FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 050682.
4 Sorafenib FDA Label
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45 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.
46 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.
47 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.
48 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.
49 Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
50 Multidrug resistance protein 2 implicates anticancer drug-resistance to sorafenib. Biol Pharm Bull. 2011;34(3):433-5.
51 Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation. Mol Cancer Ther. 2010 Feb;9(2):319-26.
52 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.
53 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
54 Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma
55 Rlip76 transports sunitinib and sorafenib and mediates drug resistance in kidney cancer. Int J Cancer. 2010 Mar 15;126(6):1327-38.
56 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.
57 Ontogeny and sorafenib metabolism. Clin Cancer Res. 2012 Oct 15;18(20):5788-95.
58 Drug Interactions Flockhart Table
59 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.
60 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.
61 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.
62 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.
63 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.
64 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.
65 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.
66 Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines. BMC Cancer. 2012 Sep 10;12:402.
67 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.
68 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.
69 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.
70 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.
71 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.
72 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.
73 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.
74 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.
75 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.
76 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.
77 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.
78 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.
79 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.
80 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.
81 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.
82 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.
83 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.
84 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.
85 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.
86 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.
87 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.
88 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.
89 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.
90 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.
91 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.
92 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.
93 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.
94 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.
95 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.
96 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.
97 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.
98 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.
99 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.
100 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.
101 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.
102 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.
103 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.
104 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.
105 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.
106 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.
107 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.
108 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.