Natural Product (NP) Details

General Information of the NP (ID: NP8606)
Name
Fisetin
Synonyms
2-(3,4-Dihydroxyphenyl)-3,7-dihydroxy-4H-chromen-4-one; 5-Desoxyquercetin; Fustel; Cotinin; Viset; 3,3',4',7-Tetrahydroxyflavone; Fisetholz; Superfustel; Fustet; Fietin; Junger fustik; 3,7,3',4'-Tetrahydroxyflavone; Ventin sumach; Zante fustic; Young fustic; Superfustel K; Ungarisches gelbholz; CI Natural Brown 1; Young fustic crystals; Bois bleu de Honqrie; BOIS bleude honqrie; CI 75620; NSC 407010; NSC 656275; 5-Deoxyquercetin; 2-(3,4-Dihydroxyphenyl)-3,7-dihydroxy-4H-1-benzopyran-4-one; Natural Brown 1; FISETIN
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Species Origin Toxicodendron succedaneum ...     Click to Show/Hide
Toxicodendron succedaneum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Anacardiaceae
Genus: Toxicodendron
Species: Toxicodendron succedaneum
Disease Pancreatic cancer [ICD-11: 2C10] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.759
 
MDCK Permeability
 -4.871
 
PAMPA
 +
 
HIA
 -
 
Distribution
VDss
 -0.743
 
PPB
 95.3%
 
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
 11.159
 
T1/2
 1.732
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
C15H10O6
PubChem CID
5281614
Canonical SMILES
C1=CC(=C(C=C1C2=C(C(=O)C3=C(O2)C=C(C=C3)O)O)O)O
InChI
1S/C15H10O6/c16-8-2-3-9-12(6-8)21-15(14(20)13(9)19)7-1-4-10(17)11(18)5-7/h1-6,16-18,20H
InChIKey
XHEFDIBZLJXQHF-UHFFFAOYSA-N
CAS Number
CAS 528-48-3
Herb ID
HBIN026506
ETMC ID
6437
SymMap ID
SMIT00327
TCMSP ID
MOL013179
TTD Drug ID
D0MF5Y
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
                 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
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAK  Molecule Info 
Pathway MAP
Up-regulation Expression BID  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP7  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model NT2-D1 CVCL_3407 Embryonal carcinoma Homo sapiens
                    In-vivo Model NT2/D1 cells (106) mixed with Matrigel were implanted into 6-week-old athymic nude mice bearing the nu/nu gene [NIH(s) (nu/nu)] and housed under pathogen-free conditions.
                    Experimental
                    Result(s)		 Addition of fisetin to cisplatin activates both the mitochondrial and the cell death receptor pathway and could be a promising regimen for the elimination of embryonal carcinoma cells.
          Cabazitaxel      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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Expression MCL1  Molecule Info 
Pathway MAP
Down-regulation Expression MKI67  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-2  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression PCNA  Molecule Info 
Pathway MAP
Down-regulation Expression PECAM1  Molecule Info 
Pathway MAP
Down-regulation Expression PRAP1  Molecule Info 
Pathway MAP
                    In-vitro Model LNCaP C4-2 CVCL_4782 Prostate carcinoma Homo sapiens
A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
PrEC Prostate cancer Homo sapiens
22Rv1 Prostate cancer Homo sapiens
                    In-vivo Model A total of 24 athymic nude male mice 6-8 weeks old were injected subcutaneously with 1*106 22Rv1 cells.
                    Experimental
                    Result(s)		 Fisetin Enhances Chemotherapeutic Effect of Cabazitaxel against Human Prostate Cancer Cells.
          Sorafenib      Renal cell 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 [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAK  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation MEK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation MEK2  Molecule Info 
Pathway MAP
Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
                    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.
          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 [5]
                    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 mTOR  Molecule Info 
Pathway MAP
Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
Up-regulation Expression PRKAA1  Molecule Info 
Pathway MAP
                    In-vitro Model SW480 CVCL_0546 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Treatment of PIK3CA-mutant cells with fisetin and 5-FU reduced the expression of PI3K, phosphorylation of AKT, mTOR, its target proteins, constituents of mTOR signaling complex and this treatment increased the phosphorylation of AMPKalpha.
          Cyclophosphamide      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 [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression PECAM1  Molecule Info 
Pathway MAP
                    In-vitro Model EA.hy 926 CVCL_3901 Healthy Homo sapiens
3LL CVCL_5653 Malignant tumors Mus musculus
NIH 3T3 CVCL_0594 Healthy Mus musculus
                    In-vivo Model Aliquots of cells (0.1 ml, 3 * 106 cells) were mixed with 0.2 ml of phenol red-free Matrigel and injected into the right flank of mice.
                    Experimental
                    Result(s)		 Fisetin not only displays in vitro and in vivo antiangiogenic properties, but also can markedly improve the in vivo antitumour effect of CPA.
          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 [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP7  Molecule Info 
Pathway MAP
Down-regulation Expression ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression ERK2  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
                    In-vitro Model MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Fisetin sensitized human pancreatic cancer cells to gemcitabine-induced cytotoxicity through inhibition of ERK-MYC signaling.
          Etoposide      Testicular 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 [8]
                    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 CCNE1  Molecule Info 
Pathway MAP
                    In-vitro Model MG-63 CVCL_0426 Osteosarcoma Homo sapiens
SaOS-2 CVCL_0548 Osteosarcoma Homo sapiens
U2OS CVCL_0042 Osteosarcoma Homo sapiens
                    Experimental
                    Result(s)		 The combination of fisetin with etoposide has higher anti-proliferative effects in osteosarcoma associated with cell cycle arrest, allowing the use of lower doses of the chemotherapeutic agent.
Target and Pathway
Target(s) Cyclin-dependent kinase 6 (CDK6)  Molecule Info  [9]
Fatty acid synthase (FASN)  Molecule Info  [10]
Plasmodium 3-oxoacyl-acyl-carrier reductase (Malaria fabG)  Molecule Info  [10]
Plasmodium enoyl-ACP reductase (Malaria fabI)  Molecule Info  [10]
Plasmodium Fatty acid synthesis protein (Malaria FabZ)  Molecule Info  [10]
BioCyc Fatty acid biosynthesis initiation Click to Show/Hide
2 Fatty acid elongation -- saturated
3 Palmitate biosynthesis
KEGG Pathway Fatty acid biosynthesis Click to Show/Hide
2 Metabolic pathways
3 Fatty acid metabolism
4 AMPK signaling pathway
5 Insulin signaling pathway
6 Cell cycle
7 p53 signaling pathway
8 PI3K-Akt signaling pathway
9 Hepatitis B
10 Measles
11 Pathways in cancer
12 Viral carcinogenesis
13 MicroRNAs in cancer
14 Pancreatic cancer
15 Glioma
16 Melanoma
17 Chronic myeloid leukemia
18 Small cell lung cancer
19 Non-small cell lung cancer
20 Fatty acid biosynthesis
21 Biotin metabolism
22 Metabolic pathways
23 Fatty acid metabolism
NetPath Pathway TGF_beta_Receptor Signaling Pathway Click to Show/Hide
Pathwhiz Pathway Fatty Acid Biosynthesis Click to Show/Hide
Pathway Interaction Database p73 transcription factor network Click to Show/Hide
2 Validated transcriptional targets of deltaNp63 isoforms
3 Coregulation of Androgen receptor activity
4 C-MYB transcription factor network
5 IL2 signaling events mediated by STAT5
6 Regulation of retinoblastoma protein
Reactome ChREBP activates metabolic gene expression Click to Show/Hide
2 Activation of gene expression by SREBF (SREBP)
3 Fatty Acyl-CoA Biosynthesis
4 Oxidative Stress Induced Senescence
5 Senescence-Associated Secretory Phenotype (SASP)
6 Oncogene Induced Senescence
7 Cyclin D associated events in G1
WikiPathways Fatty Acid Biosynthesis Click to Show/Hide
2 Nuclear Receptors Meta-Pathway
3 Liver X Receptor Pathway
4 Activation of Gene Expression by SREBP (SREBF)
5 SREBF and miR33 in cholesterol and lipid homeostasis
6 SREBP signalling
7 Metabolism of water-soluble vitamins and cofactors
8 Integration of energy metabolism
9 Fatty acid, triacylglycerol, and ketone body metabolism
10 AMPK Signaling
11 DNA Damage Response
12 G1 to S cell cycle control
13 Wnt Signaling Pathway Netpath
14 Retinoblastoma (RB) in Cancer
15 Signaling Pathways in Glioblastoma
16 Metastatic brain tumor
17 miR-targeted genes in muscle cell - TarBase
18 miR-targeted genes in lymphocytes - TarBase
19 miR-targeted genes in leukocytes - TarBase
20 miR-targeted genes in epithelium - TarBase
21 Mitotic G1-G1/S phases
22 Cell Cycle
23 miRNAs involved in DNA damage response
24 miRNA Regulation of DNA Damage Response
References
Reference 1 Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress- and mitochondrial stress-dependent pathways. Cell Death Dis. 2019 Feb 13;10(2):142.
Reference 2 Anticancer activity of a combination of cisplatin and fisetin in embryonal carcinoma cells and xenograft tumors. Mol Cancer Ther. 2011 Feb;10(2):255-68.
Reference 3 Fisetin Enhances Chemotherapeutic Effect of Cabazitaxel against Human Prostate Cancer Cells. Mol Cancer Ther. 2016 Dec;15(12):2863-2874.
Reference 4 Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. Oncotarget. 2015 Sep 29;6(29):28296-311.
Reference 5 Fisetin and 5-fluorouracil: Effective combination for PIK3CA-mutant colorectal cancer. Int J Cancer. 2019 Dec 1;145(11):3022-3032.
Reference 6 Improved antiangiogenic and antitumour activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice. Cancer Chemother Pharmacol. 2011 Aug;68(2):445-55.
Reference 7 Fisetin Enhances the Cytotoxicity of Gemcitabine by Down-regulating ERK-MYC in MiaPaca-2 Human Pancreatic Cancer Cells. Anticancer Res. 2018 Jun;38(6):3527-3533.
Reference 8 Combination of etoposide and fisetin results in anti-cancer efficiency against osteosarcoma cell models. Arch Toxicol. 2018 Mar;92(3):1205-1214.
Reference 9 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Reference 10 Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids. J Med Chem. 2006 Jun 1;49(11):3345-53.
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