Drug Details
| General Information of the Drug (ID: DR2073) | ||||
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| Name |
Sorafenib
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| Synonyms |
Nexavar; Sorafenibum; Sorafenib [INN]; Nexavar (TN); Sorafenib (INN); N-[4-Chloro-3-(trifluoromethyl)phenyl]-N'-[4-[2-(N-methylcarbamoyl)-4-pyridyloxy]phenyl]urea; N-(4-Chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea; N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcar bamoyl)-4-pyridyloxy)phenyl)urea; 4(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N(sup 2)-methylpyridine-2-carboxamide; 4-(4-((((4-Chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-2-pyridinecarboxamide; 4-(4-(3-(4-chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxyllic acid methyamide-4-methylbenzenesulfonate; 4-(4-{3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido}phenoxy)-N(sup 2)-methylpyridine-2-carboxamide; 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide; 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methyl-pyridine-2-carboxamide; 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide; 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-2-pyridinecarboxamide; 4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE; Sorafenib (Pan-TK inhibitor)
Click to Show/Hide
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| Molecular Type |
Small molecule
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| Disease | Renal cell carcinoma [ICD-11: 2C90] | Approved | [1] | |
| Structure |
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Click to Download Mol2D MOL |
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| Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product | ||||
| Formula |
C21H16ClF3N4O3
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| PubChem CID | ||||
| Canonical SMILES |
CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F
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| InChI |
1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)
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| InChIKey |
MLDQJTXFUGDVEO-UHFFFAOYSA-N
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| CAS Number |
CAS 284461-73-0
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| ChEBI ID | ||||
| GDSC | ||||
| TTD Drug ID | ||||
| DrugBank ID | ||||
| Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
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| α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug | ||||||
| Amentoflavone | Gingko biloba | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [2] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | CASP3 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CASP8 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CASP9 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CFLAR | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | ERK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MCL1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | XIAP | Molecule Info |
Pathway MAP
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| In-vivo Model | To establish the animal model, 1*107 SK-Hep1 cells were suspended in 150 ul mix-ture of serum-free DMEM and matrigel (2: 1) and inoculated subcutaneously in the right legs of nude mice. | |||||
| Experimental
Result(s) |
Amentoflavone boosts therapeutic efficacy of sorafenib through blockage of anti-apoptotic potential and induction of apoptosis in HCC in vivo. | |||||
| Apigenin | Psilotum nudum | Click to Show/Hide the Molecular Data of This NP | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [3] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Expression | BID | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CASP10 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CASP8 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CDKN1A | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CDKN2A | Molecule Info |
Pathway MAP
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| In-vitro Model | Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | ||
| Experimental
Result(s) |
The combination of apigenin and sorafenib arrested cell cycle and increased apoptotic gene expressions more than single treatment groups. | |||||
| Arsenic trioxide | Realgar and orpiment | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [4] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BECN1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BRAF | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | c-RAF | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | MAP1LC3A | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | MEK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MEK2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | mTOR | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | PIK3CB | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | PTEN | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | ULK1 | Molecule Info |
Pathway MAP
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| In-vitro Model | KG-1 | CVCL_0374 | Adult acute myeloid leukemia | Homo sapiens | ||
| U-937 | CVCL_0007 | Adult acute monocytic leukemia | Homo sapiens | |||
| Experimental
Result(s) |
The combination effect of ATO and sorafenib in AML cell lines is apoptotic and autophagy. | |||||
| Artesunate | Artemisia annua | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [5] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | c-RAF | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | ERK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | mTOR | Molecule Info |
Pathway MAP
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| In-vitro Model | SK-HEP-1 | CVCL_0525 | Hepatocellular carcinoma | Homo sapiens | ||
| SMMC-7721 | CVCL_0534 | Hepatocellular carcinoma | Homo sapiens | |||
| In-vivo Model | For a xenograft model, 1 * 107 SK-hep1 cells were injected subcutaneously into 4-6 weeks old BALB/c nu/nu mice. | |||||
| Experimental
Result(s) |
Sor and Art combination promotes a dual inhibitory effect on both RAF/MAPK and PI3K/AKT/mTOR pathways which contributes to apoptosis burst. | |||||
| Betulin | Betula pendula | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [6] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Expression | SREBF1 | Molecule Info |
Pathway MAP
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| In-vitro Model | Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | ||
| Huh-7 | CVCL_0336 | Adult hepatocellular carcinoma | Homo sapiens | |||
| SMMC-7721 | CVCL_0534 | Hepatocellular carcinoma | Homo sapiens | |||
| BEL-7402 | CVCL_5492 | Human hepatocellular carcinoma | Homo sapiens | |||
| MHCC97-L | CVCL_4973 | Adult hepatocellular carcinoma | Homo sapiens | |||
| MHCC97-H | CVCL_4972 | Adult hepatocellular carcinoma | Homo sapiens | |||
| In-vivo Model | To establish the animal model, HCC cells were injected subcutaneously into nude mice. | |||||
| Experimental
Result(s) |
SREBP-1 inhibitor Betulin enhances the antitumor effect of Sorafenib on hepatocellular carcinoma via restricting cellular glycolytic activity. | |||||
| Betulinic Acid | Rubus alceifolius | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [7] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | AKT1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-xL | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | DDIT3 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | mTOR | Molecule Info |
Pathway MAP
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| In-vitro Model | A-549 | CVCL_0023 | Lung adenocarcinoma | Homo sapiens | ||
| NCI-H358 | CVCL_1559 | Lung adenocarcinoma | Homo sapiens | |||
| A-427 | CVCL_1055 | Lung adenocarcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Combination therapy with low concentrations of sorafenib and betulinic acid had the capacity to induce high levels of cell death and abolish clonogenic activity in some NSCLC cell lines regardless of KRAS mutations. | |||||
| Bufalin | Bufo gargarizans | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [8] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | mTOR | Molecule Info |
Pathway MAP
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| In-vitro Model | PLC/PRF/5 | CVCL_0485 | Adult hepatocellular carcinoma | Homo sapiens | ||
| SMMC-7721 | CVCL_0534 | Hepatocellular carcinoma | Homo sapiens | |||
| In-vivo Model | A total of 5x106 SMMC-7721 cells in 0.2 ml phosphate-buffered saline (PBS) were injected into the right flank of each mouse (six-week old male Balb/c nude mice) to form subcutaneous tumors. | |||||
| Experimental
Result(s) |
Synergistic anti-hepatoma effect of bufalin combined with sorafenib via mediating the tumor vascular microenvironment by targeting mTOR/VEGF signaling. | |||||
| Capsaicin | Capsicum annuum | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [9] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CASP3 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | EGFR | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | PARP1 | Molecule Info |
Pathway MAP
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| In-vitro Model | LM3 | CVCL_D269 | Malignant neoplasms | Mus musculus | ||
| Hep 3B2.1-7 | CVCL_0326 | Childhood hepatocellular carcinoma | Homo sapiens | |||
| Huh-7 | CVCL_0336 | Adult hepatocellular carcinoma | Homo sapiens | |||
| In-vivo Model | Five-week-old BALB/C nude mice received a subcutaneous injection of 1*107 LM3 cells suspended in 100 uL sterile PBS into the right flank. | |||||
| Experimental
Result(s) |
Capsaicin and sorafenib combination treatment exerts synergistic anti-hepatocellular carcinoma activity by suppressing EGFR and PI3K/Akt/mTOR signaling. | |||||
| Chrysin | Tripterygium wilfordii | Click to Show/Hide the Molecular Data of This NP | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [10] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Phosphorylation | ERK1 | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | ERK2 | Molecule Info |
Pathway MAP
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| In-vitro Model | Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | ||
| Hep 3B2.1-7 | CVCL_0326 | Childhood hepatocellular carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Chrysin-induced ERK1/2 phosphorylation enhances the sensitivity of human gepatocellular carcinoma cells to sorafenib. | |||||
| Curcumin | Hellenia speciosa | Click to Show/Hide the Molecular Data of This NP | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [11] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Expression | APOA1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | FASN | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | HIF-1A | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | IL1B | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | JAK-1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | JAK-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | LDHA | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | p105 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | STAT3 | Molecule Info |
Pathway MAP
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| In-vivo Model | 1*105 of H22 tumor cells were inoculated in axillae of Kunming mice (22-25 g). | |||||
| Experimental
Result(s) |
Curcumin-enhanced antitumor effects of sorafenib via regulating the metabolism and tumor microenvironment. | |||||
| Ellagic acid | Lagerstroemia speciosa | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [12] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Activity | CASP3 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Up-regulation | ROS generation | ||||
| Up-regulation | Cytochrome c release | |||||
| In-vivo Model | Dietylnitrosamine and 2-acetylami nofluorene were used to induce HCC in male Sprague-Dawley rats. | |||||
| Experimental
Result(s) |
EA and SOR are effective on the HCC rat model through mitochondria and hepatocytes targeting. | |||||
| Fisetin | Toxicodendron succedaneum | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [13] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | AKT1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BAK | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CASP3 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | ERK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | ERK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MCL1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | MEK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | MEK2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | mTOR | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | PARP1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | PIK3CB | Molecule Info |
Pathway MAP
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| In-vitro Model | A-375 | CVCL_0132 | Amelanotic melanoma | Homo sapiens | ||
| RPMI-7951 | CVCL_1666 | Melanoma | Homo sapiens | |||
| In-vivo Model | Mice were subcutaneously inoculated with 0.1ml of 2.5*106 A375 cells or 5*106 SK-MEL-28 cells (prepared in a 50ul media + 50ul matrigel) in each flank to initiate tumor growth. | |||||
| Experimental
Result(s) |
Fisetin potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. | |||||
| Kaempferol | Equisetum hyemale | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [14] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | ABCB1 | Molecule Info |
Pathway MAP
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| In-vitro Model | Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | ||
| N1S1 | Hepatocellular carcinoma | Rattus norvegicus | ||||
| Experimental
Result(s) |
Kaempferol-mediated sensitization enhances chemotherapeutic efficacy of sorafenib against hepatocellular carcinoma. | |||||
| Luteolin | Abrus precatorius | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [15] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | JNK1 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | PARP1 | Molecule Info |
Pathway MAP
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| In-vitro Model | Hep 3B2.1-7 | CVCL_0326 | Childhood hepatocellular carcinoma | Homo sapiens | ||
| SMMC-7721 | CVCL_0534 | Hepatocellular carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Luteolin and sorafenib combination kills human hepatocellular carcinoma cells through apoptosis potentiation and JNK activation. | |||||
| Magnolol | Magnolia officinalis | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [16] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | AKT1 | Molecule Info |
Pathway MAP
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| In-vitro Model | SK-HEP-1 | CVCL_0525 | Hepatocellular carcinoma | Homo sapiens | ||
| Hep 3B2.1-7 | CVCL_0326 | Childhood hepatocellular carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
AKT inhibition is associated with magnolol-enhanced the therapeutic effect of sorafenib in HCC. | |||||
| Metformin | Galega officinalis | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [17] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Expression | PRKAA2 | Molecule Info |
Pathway MAP
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| In-vitro Model | HTh74 | CVCL_6288 | Thyroid gland anaplastic carcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Sorafenib and metformin synergistically decreased the proliferation of ATC cell lines and the outgrowth of their derived cancer stem cells. | |||||
| Nobiletin | Ageratum conyzoides | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [18] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CDKN1A | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | RB1 | Molecule Info |
Pathway MAP
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| In-vitro Model | PC-3 | CVCL_0035 | Prostate carcinoma | Homo sapiens | ||
| Experimental
Result(s) |
NOB and SOR combination was more effective than SOR and NOB alone and reduced the exposure time for SOR and NOB in PC-3 cells. NOB and SOR combination significantly caused much more apoptotic cell death and cell cycle arrest at G0/G1 phase by up-regulation of Bax, Rb1, and CDKN1A levels in PC-3 cells. | |||||
| Picropodophyllin | Dysosma majoensis | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [19] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| In-vitro Model | HLF | CVCL_2947 | Adult hepatocellular carcinoma | Homo sapiens | ||
| PLC/PRF/5 | CVCL_0485 | Adult hepatocellular carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells. | |||||
| Platycodin D | Platycodon grandiflorum | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [20] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Ubiquitination | AKT1 | Molecule Info |
Pathway MAP
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| In-vitro Model | PC-3 | CVCL_0035 | Prostate carcinoma | Homo sapiens | ||
| DU145 | CVCL_0105 | Prostate carcinoma | Homo sapiens | |||
| In-vivo Model | PC3 cells (shRNA-FOXO3a cells and MOCK cells) were injected subcutaneously into the left inguinal area of nude mice (BALB/c, nu/nu, male, 6-8 weeks old). | |||||
| Experimental
Result(s) |
The combination of Platycodin D and sorafenib may exert potent anti-cancer effects specifically via FOXO3a. | |||||
| Pterostilbene | Vitis vinifera | Click to Show/Hide the Molecular Data of This NP | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [21] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
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| Molecule(s)
Regulation |
Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP9 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CCND1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CDK2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CDK4 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CDK6 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | MAP1LC3A | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | PARP1 | Molecule Info |
Pathway MAP
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| In-vitro Model | NCI-N87 | CVCL_1603 | Gastric tubular adenocarcinoma | Homo sapiens | ||
| MKN45 | CVCL_0434 | Gastric adenocarcinoma | Homo sapiens | |||
| In-vivo Model | N87 cells (3*105 cells) were suspended in 0.1 mL of PBS and inoculated subcutaneously into the right flank of five-week-old male BALB/c nude mice. | |||||
| Experimental
Result(s) |
PET enhanced sorafenib's antitumour effects against GAC through inhibiting cell proliferation, inducing autophagy and promoting apoptosis. | |||||
| Resveratrol | Gnetum parvifolium | Click to Show/Hide the Molecular Data of This NP | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [22] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Expression | APAF1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP9 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CCNB1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CCND1 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | PARP1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TP53 | Molecule Info |
Pathway MAP
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| In-vitro Model | MCF-7 | CVCL_0031 | Invasive breast carcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Resveratrol enhances the efficacy of sorafenib mediated apoptosis in human breast cancer MCF7 cells through ROS, cell cycle inhibition, caspase 3 and PARP cleavage. | |||||
| Rottlerin | Mallotus philippinensis | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [23] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Experimental
Result(s) |
Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. | |||||
| Silibinin | Carduus marianus | Click to Show/Hide the Molecular Data of This NP | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [24] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | KLF4 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MCL1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | NANOG | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | STAT3 | Molecule Info |
Pathway MAP
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| In-vitro Model | SMMC-7721 | CVCL_0534 | Hepatocellular carcinoma | Homo sapiens | ||
| BEL-7402 | CVCL_5492 | Human hepatocellular carcinoma | Homo sapiens | |||
| BEL-7404 | CVCL_6568 | Human hepatocellular carcinoma | Homo sapiens | |||
| Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | |||
| MHCC97-H | CVCL_4972 | Adult hepatocellular carcinoma | Homo sapiens | |||
| MHCC97-L | CVCL_4973 | Adult hepatocellular carcinoma | Homo sapiens | |||
| HCCLM3 | CVCL_6832 | Adult hepatocellular carcinoma | Homo sapiens | |||
| Hepa 1-6 | CVCL_0327 | Hepatocellular carcinoma of the mouse | Mus musculus | |||
| H22 | CVCL_H613 | Hepatocellular carcinoma of the mouse | Mus musculus | |||
| In-vivo Model | Athymic nude mice or male C57BL/6 mice (aged 4-6 weeks and weighing 16-18g) were injected with Bel-7404 cells or Hepa 1-6 cells subcutaneously in the right foreleg (4*106 cells/mouse). | |||||
| Experimental
Result(s) |
Combined treatment with sorafenib and silibinin synergistically targets both HCC cells and cancer stem cells by enhanced inhibition of the phosphorylation of STAT3/ERK/AKT. | |||||
| Sulforaphane | Brassica oleracea | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [25] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | p105 | Molecule Info |
Pathway MAP
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| In-vitro Model | BxPC-3 | CVCL_0186 | Pancreatic ductal adenocarcinoma | Homo sapiens | ||
| MIA PaCa-2 | CVCL_0428 | Pancreatic ductal adenocarcinoma | Homo sapiens | |||
| Experimental
Result(s) |
SF completely eradicated SO-induced NF-KappaB binding, which was associated with abrogated clonogenicity, spheroid formation, ALDH1 activity, migratory capacity, and induction of apoptosis. | |||||
| Tanshinone IIA | Salvia miltiorrhiza | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [26] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
|||||
| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | STAT3 | Molecule Info |
Pathway MAP
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| In-vitro Model | Huh-7 | CVCL_0336 | Adult hepatocellular carcinoma | Homo sapiens | ||
| Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Tan-IIA combined with sorafenib or SC-1 exerted synergistic cytotoxicity in HCC cells. | |||||
| Taxifolin | Larix gmelinii | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [27] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
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| Molecule(s)
Regulation |
Down-regulation | Expression | FOXP3 | Molecule Info |
Pathway MAP
|
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| In-vitro Model | Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Sor-Tau combination led to FOXP3 down-regulation in hepatic cancer cells (HepG2) and improved therapeutic efficacy of sorafenib treated HCC. | |||||
| Triptolide | Tripterygium hypoglaucum | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [28] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
|||||
| Molecule(s)
Regulation |
Down-regulation | Activity | p105 | Molecule Info |
Pathway MAP
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| In-vitro Model | Huh-7 | CVCL_0336 | Adult hepatocellular carcinoma | Homo sapiens | ||
| PLC/PRF/5 | CVCL_0485 | Adult hepatocellular carcinoma | Homo sapiens | |||
| In-vivo Model | Athymic nude mice were injected with 5*106 HuH-7 cells subcutaneously in the right flank in 100-mL aliquots mixed with Matrigel in 1:1 ratio. | |||||
| Experimental
Result(s) |
The combination of triptolide and sorafenib was superior to either drug alone in inducing apoptosis and decreasing viability, whereas triptolide alone was sufficient to decrease nuclear factor kappaB activity. | |||||
| Ursodeoxycholic acid | Homo sapiens | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [29] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
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| Molecule(s)
Regulation |
Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP9 | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | ERK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | STAT3 | Molecule Info |
Pathway MAP
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| In-vitro Model | Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | ||
| Huh-BAT | Hepatocellular carcinoma | Homo sapiens | ||||
| Experimental
Result(s) |
Sorafenib and ursodeoxycholic combination is efficacious in treating hepatocellular carcinoma by inhibiting cell proliferation and inducing apoptosis through reactive oxygen species dependent activation of ERK and dephosphorylation of STAT3. | |||||
| Vitamin K | Medicago sativa | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [30] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
|||||
| Molecule(s)
Regulation |
Up-regulation | Expression | CDH1 | Molecule Info |
Pathway MAP
|
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| Up-regulation | Phosphorylation | ERK1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | HGFAC | Molecule Info | |||
| Up-regulation | Expression | MET | Molecule Info |
Pathway MAP
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| In-vitro Model | Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Sorafenib and vitamin K can function synergistically to inhibit the migration and proliferation of HCC cells. | |||||
| Vitamin K2 | Glycine max | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [31] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
|||||
| Molecule(s)
Regulation |
Up-regulation | Expression | CDKN1A | Molecule Info |
Pathway MAP
|
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| Down-regulation | Expression | MCL1 | Molecule Info |
Pathway MAP
|
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| In-vitro Model | Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | ||
| Hep 3B2.1-7 | CVCL_0326 | Childhood hepatocellular carcinoma | Homo sapiens | |||
| Huh-7 | CVCL_0336 | Adult hepatocellular carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Combined treatment with sorafenib and vitamin K2 can work synergistically to inhibit the growth of hepatocellular carcinoma cells. | |||||
| Withaferin A | Withania somnifera | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [32] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
|||||
| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | CASP3 | Molecule Info |
Pathway MAP
|
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| Down-regulation | Expression | PARP1 | Molecule Info |
Pathway MAP
|
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| In-vitro Model | B-CPAP | CVCL_0153 | Thyroid gland carcinoma | Homo sapiens | ||
| SW1736 | CVCL_3883 | Thyroid gland anaplastic carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Combination therapy with sorafenib + withaferin showed synergistic efficacy in papillary and anaplastic cancers in vitro with significant induction of apoptosis. | |||||
| Wogonin | Scutellaria amoena | Click to Show/Hide the Molecular Data of This NP | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [33] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
|||||
| Molecule(s)
Regulation |
Up-regulation | Cleavage | PARP1 | Molecule Info |
Pathway MAP
|
|
| In-vitro Model | Hep 3B2.1-7 | CVCL_0326 | Childhood hepatocellular carcinoma | Homo sapiens | ||
| BEL-7402 | CVCL_5492 | Human hepatocellular carcinoma | Homo sapiens | |||
| Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | |||
| SMMC-7721 | CVCL_0534 | Hepatocellular carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Combination of wogonin and sorafenib effectively kills human hepatocellular carcinoma cells through apoptosis potentiation and autophagy inhibition. | |||||
| Target and Pathway | ||||
|---|---|---|---|---|
| Target(s) | Epidermal growth factor receptor (EGFR) | Molecule Info | [34] | |
| Platelet-derived growth factor receptor beta (PDGFRB) | Molecule Info | [35] | ||
| Tyrosine-protein kinase Kit (KIT) | Molecule Info | [35] | ||
| Vascular endothelial growth factor receptor 2 (KDR) | Molecule Info | [35] | ||
| KEGG Pathway | MAPK signaling pathway | Click to Show/Hide | ||
| 2 | ErbB signaling pathway | |||
| 3 | Ras signaling pathway | |||
| 4 | Rap1 signaling pathway | |||
| 5 | Calcium signaling pathway | |||
| 6 | Cytokine-cytokine receptor interaction | |||
| 7 | HIF-1 signaling pathway | |||
| 8 | FoxO signaling pathway | |||
| 9 | Endocytosis | |||
| 10 | PI3K-Akt signaling pathway | |||
| 11 | Dorso-ventral axis formation | |||
| 12 | Focal adhesion | |||
| 13 | Adherens junction | |||
| 14 | Gap junction | |||
| 15 | Regulation of actin cytoskeleton | |||
| 16 | GnRH signaling pathway | |||
| 17 | Estrogen signaling pathway | |||
| 18 | Oxytocin signaling pathway | |||
| 19 | Epithelial cell signaling in Helicobacter pylori infection | |||
| 20 | Hepatitis C | |||
| 21 | Pathways in cancer | |||
| 22 | Proteoglycans in cancer | |||
| 23 | MicroRNAs in cancer | |||
| 24 | Pancreatic cancer | |||
| 25 | Endometrial cancer | |||
| 26 | Glioma | |||
| 27 | Prostate cancer | |||
| 28 | Melanoma | |||
| 29 | Bladder cancer | |||
| 30 | Non-small cell lung cancer | |||
| 31 | Central carbon metabolism in cancer | |||
| 32 | Choline metabolism in cancer | |||
| 33 | Hematopoietic cell lineage | |||
| 34 | Melanogenesis | |||
| 35 | Acute myeloid leukemia | |||
| 36 | HTLV-I infection | |||
| 37 | VEGF signaling pathway | |||
| NetPath Pathway | IL4 Signaling Pathway | Click to Show/Hide | ||
| 2 | EGFR1 Signaling Pathway | |||
| 3 | IL3 Signaling Pathway | |||
| 4 | KitReceptor Signaling Pathway | |||
| 5 | IL2 Signaling Pathway | |||
| Panther Pathway | Cadherin signaling pathway | Click to Show/Hide | ||
| 2 | EGF receptor signaling pathway | |||
| 3 | Angiogenesis | |||
| 4 | PDGF signaling pathway | |||
| 5 | VEGF signaling pathway | |||
| Pathway Interaction Database | LPA receptor mediated events | Click to Show/Hide | ||
| 2 | Signaling events mediated by PTP1B | |||
| 3 | Arf6 signaling events | |||
| 4 | Signaling events mediated by TCPTP | |||
| 5 | Thromboxane A2 receptor signaling | |||
| 6 | SHP2 signaling | |||
| 7 | Regulation of Telomerase | |||
| 8 | EGF receptor (ErbB1) signaling pathway | |||
| 9 | EGFR-dependent Endothelin signaling events | |||
| 10 | Posttranslational regulation of adherens junction stability and dissassembly | |||
| 11 | Direct p53 effectors | |||
| 12 | ErbB1 downstream signaling | |||
| 13 | Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling | |||
| 14 | E-cadherin signaling in keratinocytes | |||
| 15 | ErbB receptor signaling network | |||
| 16 | Internalization of ErbB1 | |||
| 17 | Stabilization and expansion of the E-cadherin adherens junction | |||
| 18 | a6b1 and a6b4 Integrin signaling | |||
| 19 | Syndecan-3-mediated signaling events | |||
| 20 | C-MYB transcription factor network | |||
| 21 | Signaling events mediated by Stem cell factor receptor (c-Kit) | |||
| 22 | Beta3 integrin cell surface interactions | |||
| 23 | S1P3 pathway | |||
| 24 | Nectin adhesion pathway | |||
| 25 | S1P1 pathway | |||
| 26 | PDGFR-beta signaling pathway | |||
| 27 | Validated targets of C-MYC transcriptional repression | |||
| 28 | PDGF receptor signaling network | |||
| 29 | HIF-2-alpha transcription factor network | |||
| 30 | VEGF and VEGFR signaling network | |||
| 31 | Integrins in angiogenesis | |||
| 32 | Signaling events mediated by VEGFR1 and VEGFR2 | |||
| 33 | Notch-mediated HES/HEY network | |||
| Reactome | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | Click to Show/Hide | ||
| 2 | SHC1 events in ERBB2 signaling | |||
| 3 | PLCG1 events in ERBB2 signaling | |||
| 4 | PIP3 activates AKT signaling | |||
| 5 | GRB2 events in EGFR signaling | |||
| 6 | GAB1 signalosome | |||
| 7 | SHC1 events in EGFR signaling | |||
| 8 | EGFR downregulation | |||
| 9 | GRB2 events in ERBB2 signaling | |||
| 10 | PI3K events in ERBB2 signaling | |||
| 11 | EGFR Transactivation by Gastrin | |||
| 12 | Constitutive Signaling by Aberrant PI3K in Cancer | |||
| 13 | Constitutive Signaling by EGFRvIII | |||
| 14 | RAF/MAP kinase cascade | |||
| 15 | Regulation of KIT signaling | |||
| 16 | Neurophilin interactions with VEGF and VEGFR | |||
| 17 | VEGF binds to VEGFR leading to receptor dimerization | |||
| 18 | Integrin cell surface interactions | |||
| 19 | EPHA-mediated growth cone collapse | |||
| 20 | VEGFA-VEGFR2 Pathway | |||
| 21 | VEGFR2 mediated cell proliferation | |||
| WikiPathways | ErbB Signaling Pathway | Click to Show/Hide | ||
| 2 | Regulation of Actin Cytoskeleton | |||
| 3 | EGF/EGFR Signaling Pathway | |||
| 4 | MAPK Signaling Pathway | |||
| 5 | Focal Adhesion | |||
| 6 | Aryl Hydrocarbon Receptor Pathway | |||
| 7 | Extracellular vesicle-mediated signaling in recipient cells | |||
| 8 | TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer | |||
| 9 | Hair Follicle Development: Cytodifferentiation (Part 3 of 3) | |||
| 10 | Bladder Cancer | |||
| 11 | Hair Follicle Development: Induction (Part 1 of 3) | |||
| 12 | Signaling by ERBB4 | |||
| 13 | Signaling by ERBB2 | |||
| 14 | Gastrin-CREB signalling pathway via PKC and MAPK | |||
| 15 | PIP3 activates AKT signaling | |||
| 16 | Nanoparticle-mediated activation of receptor signaling | |||
| 17 | Aryl Hydrocarbon Receptor | |||
| 18 | Spinal Cord Injury | |||
| 19 | Integrated Pancreatic Cancer Pathway | |||
| 20 | Gastric cancer network 2 | |||
| 21 | AGE/RAGE pathway | |||
| 22 | Signaling Pathways in Glioblastoma | |||
| 23 | Arylhydrocarbon receptor (AhR) signaling pathway | |||
| 24 | miR-targeted genes in muscle cell - TarBase | |||
| 25 | miR-targeted genes in lymphocytes - TarBase | |||
| 26 | miR-targeted genes in epithelium - TarBase | |||
| 27 | Integrated Breast Cancer Pathway | |||
| 28 | Signaling by EGFR | |||
| 29 | L1CAM interactions | |||
| 30 | Kit receptor signaling pathway | |||
| 31 | Differentiation Pathway | |||
| 32 | Signaling by SCF-KIT | |||
| 33 | Cardiac Progenitor Differentiation | |||
| 34 | Osteoblast Signaling | |||
| 35 | PDGF Pathway | |||
| 36 | Signaling by PDGF | |||
| 37 | Nifedipine Activity | |||
| 38 | Signaling by VEGF | |||
| 39 | Angiogenesis | |||
