Drug Details
| General Information of the Drug (ID: DR6166) | ||||
|---|---|---|---|---|
| Name |
Regorafenib
|
|||
| Synonyms |
BAY 73-4506; Regorafenibum; Stivarga; 4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide; BAY73-4506; Regorafenib (BAY 73-4506); UNII-24T2A1DOYB; 4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide; BAY-73-4506; 24T2A1DOYB; CHEMBL1946170; CHEBI:68647; Stivarga (TN); BAY73-4506 hydrochloride; Regorafenib [USAN:INN]; 755037-03-7
Click to Show/Hide
|
|||
| Molecular Type |
Small molecule
|
|||
| Disease | Colorectal cancer [ICD-11: 2B91] | Approved | [1] | |
| Structure |
|
Click to Download Mol2D MOL |
||
| Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product | ||||
| Formula |
C21H15ClF4N4O3
|
|||
| 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)F
|
|||
| InChI |
1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)
|
|||
| InChIKey |
FNHKPVJBJVTLMP-UHFFFAOYSA-N
|
|||
| CAS Number |
CAS 755037-03-7
|
|||
| ChEBI ID | ||||
| TTD Drug ID | ||||
| DrugBank ID | ||||
| Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
|---|---|---|---|---|---|---|
| α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug | ||||||
| Chlorogenic acid | Imperata cylindrica | 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 | [2] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
|||||
| Molecule(s)
Regulation |
Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
|
|
| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
|
||
| Down-regulation | Expression | BCL-xL | Molecule Info |
Pathway MAP
|
||
| Up-regulation | Expression | CASP7 | Molecule Info |
Pathway MAP
|
||
| In-vitro Model | PLC/PRF/5 | CVCL_0485 | Adult hepatocellular carcinoma | Homo sapiens | ||
| Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Co-treatment with Regorafenib and CGA enhanced Regorafenib action, reducing its cytotoxicity in HCC cells. | |||||
| Silibinin | Carduus marianus | 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 | [3] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
|||||
| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | AKT1 | Molecule Info |
Pathway MAP
|
|
| Down-regulation | Phosphorylation | EIF4EBP1 | Molecule Info |
Pathway MAP
|
||
| Down-regulation | Phosphorylation | S6K1 | Molecule Info |
Pathway MAP
|
||
| In-vitro Model | SW48 | CVCL_1724 | Colon adenocarcinoma | Homo sapiens | ||
| GEO | CVCL_0271 | Colon carcinoma | Homo sapiens | |||
| LIM1215 | CVCL_2574 | Colon adenocarcinoma | Homo sapiens | |||
| HCT 15 | CVCL_0292 | Colon adenocarcinoma | Homo sapiens | |||
| HCT 116 | CVCL_0291 | Colon carcinoma | Homo sapiens | |||
| SW480 | CVCL_0546 | Colon adenocarcinoma | Homo sapiens | |||
| LoVo | CVCL_0399 | Colon adenocarcinoma | Homo sapiens | |||
| SW620 | CVCL_0547 | Colon adenocarcinoma | Homo sapiens | |||
| Experimental
Result(s) |
The combined treatment with regorafenib and silybin induced synergistic anti-proliferative and apoptotic effects by blocking PI3K/AKT/mTOR intracellular pathway. | |||||
| Toosendanin | Melia azedarach | 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
|
|||||
| Molecule(s)
Regulation |
Down-regulation | Expression | DVL2 | Molecule Info |
Pathway MAP
|
|
| Up-regulation | Phosphorylation | GSK-3B | Molecule Info |
Pathway MAP
|
||
| Down-regulation | Phosphorylation | STAT3 | Molecule Info |
Pathway MAP
|
||
| Up-regulation | Expression | WWOX | Molecule Info | |||
| In-vitro Model | MHCC97-L | CVCL_4973 | Adult hepatocellular carcinoma | Homo sapiens | ||
| Experimental
Result(s) |
TSN and RGF combination (TRC) synergistically inhibited the proliferation and migration of MHCC-97L cells. The upregulation of WWOX (WW-domain containing oxidoreductase) played a vital role in the HCC cell growth treated with TRC. | |||||
| Target and Pathway | ||||
|---|---|---|---|---|
| Target(s) | Proto-oncogene c-Ret (RET) | Molecule Info | [5] | |
| Tyrosine-protein kinase Kit (KIT) | Molecule Info | [5] | ||
| Vascular endothelial growth factor receptor 2 (KDR) | Molecule Info | [5] | ||
| KEGG Pathway | Ras signaling pathway | Click to Show/Hide | ||
| 2 | Rap1 signaling pathway | |||
| 3 | Cytokine-cytokine receptor interaction | |||
| 4 | Endocytosis | |||
| 5 | PI3K-Akt signaling pathway | |||
| 6 | Hematopoietic cell lineage | |||
| 7 | Melanogenesis | |||
| 8 | Pathways in cancer | |||
| 9 | Acute myeloid leukemia | |||
| 10 | Central carbon metabolism in cancer | |||
| 11 | Thyroid cancer | |||
| 12 | VEGF signaling pathway | |||
| 13 | Focal adhesion | |||
| 14 | Proteoglycans in cancer | |||
| NetPath Pathway | IL3 Signaling Pathway | Click to Show/Hide | ||
| 2 | IL4 Signaling Pathway | |||
| 3 | KitReceptor Signaling Pathway | |||
| 4 | IL2 Signaling Pathway | |||
| Panther Pathway | Angiogenesis | Click to Show/Hide | ||
| 2 | VEGF signaling pathway | |||
| Pathway Interaction Database | C-MYB transcription factor network | Click to Show/Hide | ||
| 2 | Signaling events mediated by Stem cell factor receptor (c-Kit) | |||
| 3 | Signaling events regulated by Ret tyrosine kinase | |||
| 4 | Posttranslational regulation of adherens junction stability and dissassembly | |||
| 5 | HIF-2-alpha transcription factor network | |||
| 6 | Beta3 integrin cell surface interactions | |||
| 7 | Signaling events mediated by TCPTP | |||
| 8 | SHP2 signaling | |||
| 9 | S1P1 pathway | |||
| 10 | VEGF and VEGFR signaling network | |||
| 11 | Integrins in angiogenesis | |||
| 12 | Signaling events mediated by VEGFR1 and VEGFR2 | |||
| 13 | Notch-mediated HES/HEY network | |||
| Reactome | PIP3 activates AKT signaling | Click to Show/Hide | ||
| 2 | Regulation of KIT signaling | |||
| 3 | Constitutive Signaling by Aberrant PI3K in Cancer | |||
| 4 | RAF/MAP kinase cascade | |||
| 5 | Neurophilin interactions with VEGF and VEGFR | |||
| 6 | VEGF binds to VEGFR leading to receptor dimerization | |||
| 7 | Integrin cell surface interactions | |||
| 8 | EPHA-mediated growth cone collapse | |||
| 9 | VEGFA-VEGFR2 Pathway | |||
| 10 | VEGFR2 mediated cell proliferation | |||
| WikiPathways | Kit receptor signaling pathway | Click to Show/Hide | ||
| 2 | Differentiation Pathway | |||
| 3 | Signaling by SCF-KIT | |||
| 4 | PIP3 activates AKT signaling | |||
| 5 | Cardiac Progenitor Differentiation | |||
| 6 | miR-targeted genes in muscle cell - TarBase | |||
| 7 | miR-targeted genes in lymphocytes - TarBase | |||
| 8 | miR-targeted genes in epithelium - TarBase | |||
| 9 | SIDS Susceptibility Pathways | |||
| 10 | Dopaminergic Neurogenesis | |||
| 11 | Focal Adhesion | |||
| 12 | Nifedipine Activity | |||
| 13 | Signaling by VEGF | |||
| 14 | Angiogenesis | |||
