Natural Product (NP) Details

General Information of the NP (ID: NP6084)
Name
Resveratrol
Synonyms
Resvida; KUC104385N; R 5010; SRT 501; Cis-resveratrol; PREVENTION 8 (RESVERATROL); RM-1812; SRT-501; Trans-resveratrol; CU-01000001503-3; KSC-10-164; Resveratrol-3-sulfate; Trans-3,4',5-trihydroxystilbene; Trans-3,4′ ,5-Trihydroxystilbene; Trans-1,2-(3,4',5-Trihydroxydiphenyl)ethylene; (E)-5-(2-(4-hydroxyphenyl)ethenyl)-1,3-benzenediol
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Species Origin Gnetum parvifolium ...     Click to Show/Hide
Gnetum parvifolium
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Gnetopsida
Order: Gnetales
Family: Gnetaceae
Genus: Gnetum
Species: Gnetum parvifolium
Myristica fragrans
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Magnoliales
Family: Myristicaceae
Genus: Myristica
Species: Myristica fragrans
Vitis amurensis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Vitales
Family: Vitaceae
Genus: Vitis
Species: Vitis amurensis
Disease Rheumatoid arthritis [ICD-11: FA20] Phase 3 [1]
Vasculitis [ICD-11: 4A44] Phase 3 [1]
Colorectal cancer [ICD-11: 2B91] Discontinued in Phase 2 [2]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.917
 
MDCK Permeability
 -4.774
 
PAMPA
 -
 
HIA
 - - -
 
Distribution
VDss
 0.101
 
PPB
 88.6%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 +++
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 +++
CYP3A4 inhibitor
 +++
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 +++
HLM Stability
 - -
 
Excretion
CLplasma
 9.035
 
T1/2
 1.456
Toxicity
DILI
 - - -
 
Rat Oral Acute Toxicity
 - -
 
FDAMDD
 ++
 
Respiratory
 -
 
Human Hepatotoxicity
 +
 
Ototoxicity
 - -
 
Drug-induced Nephrotoxicity
 - - -
 
Drug-induced Neurotoxicity
 -
 
Hematotoxicity
 - - -
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C14H12O3
PubChem CID
445154
Canonical SMILES
C1=CC(=CC=C1C=CC2=CC(=CC(=C2)O)O)O
InChI
1S/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1+
InChIKey
LUKBXSAWLPMMSZ-OWOJBTEDSA-N
CAS Number
CAS 501-36-0
Herb ID
HBIN042111
ETMC ID
2769
SymMap ID
SMIT00323
TCMSP ID
MOL012744
TTD Drug ID
D0U3EP
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Cisplatin      Bladder cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Up-regulation Expression GJA1  Molecule Info 
Pathway MAP
                    In-vitro Model K1735 CVCL_F828 Mouse melanoma Mus musculus
B16-F10 CVCL_0159 Mouse melanoma Mus musculus
                    In-vivo Model Animal models were constructed by inoculating subcutaneously with 106 B16F10 cells in male C57BL/6 mice.
                    Experimental
                    Result(s)		 Resveratrol enhances chemosensitivity in mouse melanoma model through connexin 43 upregulation.
          Temozolomide      Brain cancer     Click to Show/Hide the Molecular Data of This Drug
                 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 BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression GFAP  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation PRKAA1  Molecule Info 
Pathway MAP
                    In-vitro Model SHG-44 CVCL_6728 Astrocytoma Homo sapiens
                    In-vivo Model SHG44 cells (5*105 cells per mouse) in 5 uL of Hanks' solution were injected intracranially into the right caudate nucleus of 6- to 8-week-old female nude mice.
                    Experimental
                    Result(s)		 Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway.
          Trastuzumab      Breast cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression HER2  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
T-47D CVCL_0553 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Herceptin / resveratrol combinations improved the cytotoxic profile of herceptin in both T47D and MCF-7 breast cancer cell lines.
          Cetuximab      Colorectal cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression PLAUR  Molecule Info 
Pathway MAP
                    In-vitro Model SAS CVCL_1675 Tongue squamous cell carcinoma Homo sapiens
Sa3 CVCL_8063 Gingival squamous cell carcinoma Homo sapiens
HSC-3 CVCL_1288 Tongue squamous cell carcinoma Homo sapiens
                    In-vivo Model SAS-R or Sa3-R cells (1*106) were injected subcutaneously into the backs of the female athymic nude mice.
                    Experimental
                    Result(s)		 Resveratrol targets Urokinase-type plasminogen activator receptor expression to overcome cetuximab-resistance in oral squamous cell carcinoma.
          Nutlin-3      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model A2780 CVCL_0134 Ovarian endometrioid adenocarcinoma Homo sapiens
A2780/CP70 CVCL_0135 Ovarian endometrioid adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Treatment of ovarian cancer cells with nutlin-3 and resveratrol combination leads to apoptosis via caspase activation.
          TNF-related apoptosis inducing ligand      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BBC3  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation p105  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
HCC15 CVCL_2057 Lung squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-kappaB signaling.
          hu14.18-IL2 immunicytokine      Melanoma     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Up-regulation Expression GD2  Molecule Info 
Pathway MAP
                    In-vitro Model NXS2 Neuroblastoma Rattus norvegicus
                    In-vivo Model NXS2 tumors were induced in A/J mice by injecting 2*106 cells in 100 mcL PBS subcutaneously on the left flank proximal to the spleen.
                    Experimental
                    Result(s)		 RV in combination with IC provided an enhanced anti-tumor treatment in preclinical model as it lowered the tumor burden and increased survival.
          Rapamycin      Multiple myeloma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation S6K1  Molecule Info 
Pathway MAP
                    In-vitro Model KTC-1 CVCL_6300 Thyroid gland carcinoma Homo sapiens
TPC-1 CVCL_6298 Thyroid gland papillary carcinoma Homo sapiens
                    In-vivo Model KTC-1 and TPC-1 cells in logarithmic growth phase were subcutaneously inoculated into the right armpit of Nude BALB/c mice (5*106 cells/mouse).
                    Experimental
                    Result(s)		 Resveratrol sensitizes the anti-tumor effects of rapamycin and the PI3K/AKT/mTOR signaling is involved.
          Clofarabine      Myelodysplastic syndrome     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression MET  Molecule Info 
Pathway MAP
Down-regulation Expression PSG1  Molecule Info 
Pathway MAP
                    In-vitro Model MeT-5A CVCL_3749 Healthy Homo sapiens
MSTO-211H CVCL_1430 Pleural biphasic mesothelioma Homo sapiens
                    Experimental
                    Result(s)		 The synergistic antiproliferative effect of resveratrol and clofarabine is linked to the inhibition of Akt and Sp1 activities.
          Raloxifene      Osteoporosis     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of Res and Ral via increased expression of apoptotic genes including Bax, p53 and caspase-3 and caspase-8 is able to promote apoptosis as a mitochondrial dependent pathway in MCF7 and MDA-MB-231.
          ABT-737      Ovarian cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model MOLT-4 CVCL_0013 Adult T acute lymphoblastic leukemia Homo sapiens
                    Experimental
                    Result(s)		 Combination of ABT-737 and resveratrol enhances DNA damage and apoptosis in human T-cell acute lymphoblastic leukemia MOLT-4 cells.
          Melphalan      Ovarian cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP7  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression CCNA1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation CDK2  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation RAD53  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Resveratrol chemosensitizes breast cancer cells to melphalan by cell cycle arrest.
          Flutamide      Prostate cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Down-regulation Expression AR  Molecule Info 
Pathway MAP
                    In-vitro Model LNCaP CVCL_0395 Prostate carcinoma Homo sapiens
PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
DU145 CVCL_0105 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combination of resveratrol with flutamide had a synergistic effect on down-regulation of androgen receptor (AR).
          Sorafenib      Renal cell carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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
                    Molecule(s)
                    Regulation		 Up-regulation Expression APAF1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    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.
          Celecoxib      Rheumatoid arthritis     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    In-vivo Model Mammary carcinogenesis was initiated with two intra peritoneal doses (50 mg/kg body weight each) of N-methyl-N-nitrosourea (NMU) dissolved in a physiological NaCl solution.
                    Experimental
                    Result(s)		 Resveratrol enhances the chemopreventive effect of celecoxib in chemically induced breast cancer in rats.
          5-fluorouracil      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model TE-1 CVCL_1759 Esophageal squamous cell carcinoma Homo sapiens
A-431 CVCL_0037 Skin squamous cell carcinoma Homo sapiens
                    In-vivo Model The topical use of 7, 12-dimethylbenz[a]anthracene (DMBA) in acetone (150 mg/mouse) served as a tumor initiator in swiss albino mice.
                    Experimental
                    Result(s)		 Resveratrol synergistically augments anti-tumor effect of 5-FU in vitro and in vivo by increasing S-phase arrest and tumor apoptosis.
          Doxorubicin      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Down-regulation Expression MSH3  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    In-vivo Model MCF-7/adr cells (5*105 cells in 0.1mL) suspended in serum-free medium containing 50% Matrigel were inoculated subcutaneously through 25-gauge needles into the right flank of each nude mouse.
                    Experimental
                    Result(s)		 Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin.
          Gemcitabine      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model AsPC-1 CVCL_0152 Pancreatic ductal adenocarcinoma Homo sapiens
MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
MDA-Panc-28 CVCL_3917 Pancreatic adenocarcinoma Homo sapiens
                    In-vivo Model A small left abdominal flank incision was made in male athymic nu/nu mice, and MIA PaCa-2 cells (2*106) in 50 uL PBS were injected into the subcapsular region of the pancreas.
                    Experimental
                    Result(s)		 Resveratrol can potentiate the effects of gemcitabine through suppression of markers of proliferation, invasion, angiogenesis and metastasis.
          Mitomycin C      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    Molecule(s)
                    Regulation		 Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Down-regulation Expression CCNB2  Molecule Info 
Pathway MAP
Down-regulation Expression CDK1  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
                    In-vitro Model Cell lines established from resected colorectal tumor specimens Colorectal cancer Homo sapiens
                    Experimental
                    Result(s)		 Resveratrol enhances mitomycin C-mediated suppression of human colorectal cancer cell proliferation by up-regulation of p21WAF1/CIP1.
          Etoposide      Testicular carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    Molecule(s)
                    Regulation		 Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of resveratrol and etoposide showed synergistic anti-proliferative effect on hepatocellular carcinoma cells.
          Ivacaftor      Cystic fibrosis     Click to Show/Hide the Molecular Data of This Drug
                 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
                    In-vitro Model Cells derived from cystic fibrosis patients Cystic fibrosis Homo sapiens
Fisher rat thyroid cells Healthy Rattus norvegicus
                    Experimental
                    Result(s)		 Additive improvement in G551D CFTR-mediated Cl-secretion suggests that resveratrol could enhance ivacaftor therapy in these patients and improve CF-related rhinosinusitis.
          Thymidine kinase/ganciclovir      Cytomegaloviral disease     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    In-vitro Model B16 CVCL_F936 Mouse melanoma Mus musculus
                    In-vivo Model B16TK cells and B16 cells were mixed at a 3:7 ratio and subcutaneously inoculated the right flank of the pathogen-free C57BL/6 J mice (18-22 g).
                    Experimental
                    Result(s)		 Resveratrol could synergistically enhance the killing effect of TK/GCV suicide gene system in melanoma B16 cells and transplanted melanoma.
          Imatinib      Mantle cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 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
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Treatment with resveratrol (concentration-dependent) and imatinib mesylate showed significantly greater inhibition of K562 cell growth and a higher apoptosis rate of K562 cells than imatinib mesylate medication alone and the control group.
          Roscovitine      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Resveratrol modulates roscovitine-mediated cell cycle arrest of human MCF-7 breast cancer cells.
Target and Pathway
Target(s) NAD-dependent deacetylase sirtuin-1 (SIRT1)  Molecule Info  [27]
Prostaglandin G/H synthase 1 (COX-1)  Molecule Info  [28]
BioCyc C20 prostanoid biosynthesis Click to Show/Hide
KEGG Pathway FoxO signaling pathway Click to Show/Hide
2 AMPK signaling pathway
3 Glucagon signaling pathway
4 Amphetamine addiction
5 MicroRNAs in cancer
6 Arachidonic acid metabolism
7 Metabolic pathways
8 Platelet activation
9 Serotonergic synapse
NetPath Pathway TGF_beta_Receptor Signaling Pathway Click to Show/Hide
Panther Pathway p53 pathway Click to Show/Hide
2 Inflammation mediated by chemokine and cytokine signaling pathway
Pathwhiz Pathway Arachidonic Acid Metabolism Click to Show/Hide
Pathway Interaction Database p73 transcription factor network Click to Show/Hide
2 Signaling events mediated by HDAC Class III
3 E2F transcription factor network
4 HIF-2-alpha transcription factor network
5 Signaling events mediated by HDAC Class I
6 FoxO family signaling
7 Regulation of Androgen receptor activity
8 Regulation of retinoblastoma protein
Reactome RORA activates gene expression Click to Show/Hide
2 Regulation of HSF1-mediated heat shock response
3 Circadian Clock
WikiPathways Integrated Pancreatic Cancer Pathway Click to Show/Hide
2 SREBF and miR33 in cholesterol and lipid homeostasis
3 Integrated Breast Cancer Pathway
4 SREBP signalling
5 Androgen receptor signaling pathway
6 Prostaglandin Synthesis and Regulation
7 Arachidonic acid metabolism
8 Phase 1 - Functionalization of compounds
9 Eicosanoid Synthesis
10 Selenium Micronutrient Network
References
Reference 1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Reference 2 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018787)
Reference 3 Resveratrol Enhances Chemosensitivity in Mouse Melanoma Model Through Connexin 43 Upregulation. Environ Toxicol. 2015 Jul 8;30(8):877-86.
Reference 4 Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway. CNS Neurosci Ther. 2012 Jul;18(7):536-46.
Reference 5 The chemomodulatory effects of resveratrol and didox on herceptin cytotoxicity in breast cancer cell lines. Sci Rep. 2015 Jul 9;5:12054.
Reference 6 Resveratrol Targets Urokinase-Type Plasminogen Activator Receptor Expression to Overcome Cetuximab-Resistance in Oral Squamous Cell Carcinoma. Sci Rep. 2019 Aug 21;9(1):12179.
Reference 7 Treatment of ovarian cancer cells with nutlin-3 and resveratrol combination leads to apoptosis via caspase activation. J Med Food. Jan-Feb 2011;14(1-2):46-52.
Reference 8 Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-kappaB signaling. Life Sci. 2018 Sep 1;208:208-220.
Reference 9 The anti-tumor effect of resveratrol alone or in combination with immunotherapy in a neuroblastoma model. Cancer Immunol Immunother. 2011 May;60(5):731-8.
Reference 10 Resveratrol potentiates the anti-tumor effects of rapamycin in papillary thyroid cancer: PI3K/AKT/mTOR pathway involved. Arch Biochem Biophys. 2020 Aug 15;689:108461.
Reference 11 Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells. Food Chem Toxicol. 2013 Feb;52:61-8.
Reference 12 Apoptosis induction in human breast cancer cell lines by synergic effect of raloxifene and resveratrol through increasing proapoptotic genes. Life Sci. 2018 Jul 15;205:45-53.
Reference 13 Combination of ABT-737 and resveratrol enhances DNA damage and apoptosis in human T-cell acute lymphoblastic leukemia MOLT-4 cells. Toxicol In Vitro. 2017 Aug;42:38-46.
Reference 14 Resveratrol chemosensitizes breast cancer cells to melphalan by cell cycle arrest. J Cell Biochem. 2012 Aug;113(8):2586-96.
Reference 15 Combination of resveratrol and antiandrogen flutamide has synergistic effect on androgen receptor inhibition in prostate cancer cells. Anticancer Res. 2011 Oct;31(10):3323-30.
Reference 16 Resveratrol enhances the efficacy of sorafenib mediated apoptosis in human breast cancer MCF7 cells through ROS, cell cycle inhibition, caspase 3 and PARP cleavage. Biomed Pharmacother. 2016 Dec;84:1906-1914.
Reference 17 Resveratrol enhances the chemopreventive effect of celecoxib in chemically induced breast cancer in rats. Eur J Cancer Prev. 2014 Nov;23(6):506-13.
Reference 18 Resveratrol synergistically augments anti-tumor effect of 5-FU in vitro and in vivo by increasing S-phase arrest and tumor apoptosis. Exp Biol Med (Maywood). 2015 Dec;240(12):1672-81.
Reference 19 Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin. Biochim Biophys Acta. 2014 Jan;1840(1):615-25.
Reference 20 Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer. 2010 Jul 15;127(2):257-68.
Reference 21 Resveratrol enhances mitomycin C-mediated suppression of human colorectal cancer cell proliferation by up-regulation of p21WAF1/CIP1. Anticancer Res. 2014 Oct;34(10):5439-46.
Reference 22 Synergistic anti-proliferative effect of resveratrol and etoposide on human hepatocellular and colon cancer cell lines. Eur J Pharmacol. 2013 Oct 15;718(1-3):34-40.
Reference 23 Resveratrol and ivacaftor are additive G551D CFTR-channel potentiators: therapeutic implications for cystic fibrosis sinus disease. Int Forum Allergy Rhinol. 2019 Jan;9(1):100-105.
Reference 24 Synergistic inhibitory effect of resveratrol and TK/GCV therapy on melanoma cells. J Cancer Res Clin Oncol. 2020 Jun;146(6):1489-1499.
Reference 25 Inhibition of human chronic myelogenous leukemia K562 cell growth following combination treatment with resveratrol and imatinib mesylate. Genet Mol Res. 2015 Jun 11;14(2):6413-8.
Reference 26 Resveratrol modulates roscovitine-mediated cell cycle arrest of human MCF-7 breast cancer cells. Food Chem Toxicol. 2008 Apr;46(4):1327-33.
Reference 27 Sirtuin modulators: an updated patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):5-15.
Reference 28 Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2: a mechanistic approach to the design of COX-1 selective agents. J Biol Chem. 2004 May 21;279(21):22727-37.
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