Natural Product (NP) Details

General Information of the NP (ID: NP2717)
Name
Tangeretin
Synonyms
Tangeritin; Ponkanetin; Pentamethoxyflavone; 4',5,6,7,8-Pentamethoxyflavone; 5,6,7,8,4'-Pentamethoxyflavone; Tangeretin (6CI); 4H-1-Benzopyran-4-one, 5,6,7,8-tetramethoxy-2-(4-methoxyphenyl)-; 5,6,7,8-tetramethoxy-2-(4-methoxyphenyl)chromen-4-one; UNII-I4TLA1DLX6; NSC 53909; 5,6,7,8-Tetramethoxy-2-(4-methoxyphenyl)-4-benzopyrone; 5,6,7,8-tetramethoxy-2-(4-methoxyphenyl)-4H-chromen-4-one; I4TLA1DLX6; CHEMBL73930; MLS002667634; CHEBI:9400; 4H-1-Benzopyran-4-one, 5,6,7,8-tetramethoxy-2-(p-methoxyphenyl)-; NSC53909; Flavone, 4',5,6,7,8-pentamethoxy- (7CI,8CI); MFCD00017438; NSC-53909; Flavone, 5,6,7,8,4'-pentamethoxy; Tangeritin; NSC53909; NSC618905; 5,6,7,8-tetramethoxy-2-(4-methoxyphenyl)-4H-1-benzopyran-4-one; EINECS 207-570-1; BRN 0351695; AI3-23869; 4',5,6,7,8-pentamethoxy-flavone; Tangeretin (Tangeritin); 2-(4-Methoxyphenyl)-5,6,7,8-tetramethoxy-4H-1-benzopyran-4-one; Spectrum2_001698; Spectrum3_000920; Spectrum4_001019; SCHEMBL19740; KBioGR_001517; 5-18-05-00491 (Beilstein Handbook Reference); SPECTRUM1505269; SPBio_001656; Tangeretin, analytical standard; MEGxp0_001011; Tangeretin, >=95% (HPLC); ACon1_001263; KBio3_001900; DTXSID30197417; Flavone,5,6,7,8-pentamethoxy-; HMS3651A22; HY-N0133; ZINC1531699; 4'',5,6,7,8-pentamethoxyflavone; 4H-1-Benzopyran-4-one, 2-(4-methoxyphenyl)-5,6,7,8-tetramethoxy-; 5,6,7,8,4''-Pentamethoxyflavone; BDBM50209218; CCG-38782; CT0015; LMPK12111443; NSC618905; s2363; AKOS015895209; AC-1699; CS-5484; MCULE-1727108016; NSC 618905; NSC-618905; SDCCGMLS-0066766.P001; Flavone, 4',5,6,7,8-pentamethoxy-; NCGC00095850-01; NCGC00095850-02; NCGC00169520-01; AK168079; AS-11637; NCI60_004330; SMR001557394; ST097546; AB0010469; FT-0632194; N2077; SW219232-1; C10190; K-9174; 481T538; SR-05000002625; CU-01000013437-2; Q-100525; Q1748737; SR-05000002625-1; BRD-K25186396-001-02-1; BRD-K25186396-001-04-7; 4H-1-Benzopyran-4-one,6,7,8-tetramethoxy-2-(4-methoxyphenyl)-; 4H-1-Benzopyran-4-one,6,7,8-tetramethoxy-2-(p-methoxyphenyl)-; 4H-1-Benzopyran-4-one, 5,6,7,8-tetra-methoxy-2-(4-methoxyphenyl)-; 5,6,7,8-Tetramethoxy-2-(4-methoxyphenyl)-4H-1-benzopyran-4-one, 9CI
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Species Origin Citrus reticulata ...     Click to Show/Hide
Citrus reticulata
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Rutaceae
Genus: Citrus
Species: Citrus reticulata
Disease Breast cancer [ICD-11: 2C60] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.5
 
MDCK Permeability
 -4.554
 
PAMPA
 - - -
 
HIA
 - - -
 
Distribution
VDss
 -0.258
 
PPB
 93.4%
 
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
 6.882
 
T1/2
 0.904
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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Formula
C20H20O7
PubChem CID
68077
Canonical SMILES
COC1=CC=C(C=C1)C2=CC(=O)C3=C(O2)C(=C(C(=C3OC)OC)OC)OC
InChI
1S/C20H20O7/c1-22-12-8-6-11(7-9-12)14-10-13(21)15-16(23-2)18(24-3)20(26-5)19(25-4)17(15)27-14/h6-10H,1-5H3
InChIKey
ULSUXBXHSYSGDT-UHFFFAOYSA-N
CAS Number
CAS 481-53-8
Herb ID
HBIN045469
ETMC ID
1349
SymMap ID
SMIT00621
TCMSP ID
MOL005814
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          5-fluorouracil      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 [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 BID  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Down-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation RB1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation TP53  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HCT 15 CVCL_0292 Colon adenocarcinoma Homo sapiens
KM12-C CVCL_9547 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of TAN and 5-FU significantly accelerates apoptosis via JNK mediated pathway.
Target and Pathway
Target(s) Multidrug resistance protein 1 (ABCB1)  Molecule Info  [3]
Multidrug resistance protein 2 (ABCC2)  Molecule Info  [4]
Ribosomal protein S6 kinase beta-1 (S6K1)  Molecule Info  [5]
KEGG Pathway ABC transporters Click to Show/Hide
2 Bile secretion
3 MicroRNAs in cancer
4 ErbB signaling pathway
5 HIF-1 signaling pathway
6 mTOR signaling pathway
7 PI3K-Akt signaling pathway
8 AMPK signaling pathway
9 TGF-beta signaling pathway
10 Fc gamma R-mediated phagocytosis
11 Insulin signaling pathway
12 Proteoglycans in cancer
13 Acute myeloid leukemia
14 Choline metabolism in cancer
NetPath Pathway IL2 Signaling Pathway Click to Show/Hide
2 TCR Signaling Pathway
Panther Pathway Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade Click to Show/Hide
2 PDGF signaling pathway
3 PI3 kinase pathway
4 p53 pathway by glucose deprivation
5 CCKR signaling map ST
Pathwhiz Pathway Leucine Stimulation on Insulin Signaling Click to Show/Hide
Pathway Interaction Database HIF-1-alpha transcription factor network Click to Show/Hide
2 Insulin Pathway
3 IL4-mediated signaling events
4 CDC42 signaling events
5 Angiopoietin receptor Tie2-mediated signaling
6 Regulation of Telomerase
7 mTOR signaling pathway
8 IGF1 pathway
9 IL2 signaling events mediated by PI3K
10 Integrins in angiogenesis
11 RXR and RAR heterodimerization with other nuclear receptor
12 Signaling events mediated by Stem cell factor receptor (c-Kit)
13 a6b1 and a6b4 Integrin signaling
14 TGF-beta receptor signaling
Reactome ABC-family proteins mediated transport Click to Show/Hide
2 mTORC1-mediated signalling
WikiPathways Nuclear Receptors in Lipid Metabolism and Toxicity Click to Show/Hide
2 NRF2 pathway
3 Irinotecan Pathway
4 Drug Induction of Bile Acid Pathway
5 Codeine and Morphine Metabolism
6 Abacavir transport and metabolism
7 Multi Drug Resistance Protein 1 (Glycoprotein 1) Regulation
8 Integrated Pancreatic Cancer Pathway
9 Allograft Rejection
10 ErbB Signaling Pathway
11 Interferon type I signaling pathways
12 G13 Signaling Pathway
13 IL-2 Signaling Pathway
14 Insulin Signaling
15 Cytoplasmic Ribosomal Proteins
16 EGF/EGFR Signaling Pathway
17 IL-4 Signaling Pathway
18 IL-6 signaling pathway
19 Kit receptor signaling pathway
20 Apoptosis-related network due to altered Notch3 in ovarian cancer
21 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
22 BDNF signaling pathway
23 Interleukin-11 Signaling Pathway
24 FSH signaling pathway
25 Leptin signaling pathway
26 TSH signaling pathway
27 Signaling by Insulin receptor
28 TOR Signaling
29 AMPK Signaling
30 IL-5 Signaling Pathway
References
Reference 1 Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1-mediated metabolism to the product 4' hydroxy tangeretin. Toxicol In Vitro. 2018 Aug;50:274-284.
Reference 2 Synergistic therapy with tangeretin and 5-fluorouracil accelerates the ROS/JNK mediated apoptotic pathway in human colorectal cancer cell. Food Chem Toxicol. 2020 Sep;143:111529.
Reference 3 Tangeretin, a citrus pentamethoxyflavone, antagonizes ABCB1-mediated multidrug resistance by inhibiting its transport function. Pharmacol Res. 2016 Aug;110:193-204.
Reference 4 Role of tangeretin as a potential bioavailability enhancer for silybin: Pharmacokinetic and pharmacological studies. Pharmacol Res. 2018 Feb;128:153-166.
Reference 5 Tangeretin and its metabolite 4'-hydroxytetramethoxyflavone attenuate EGF-stimulated cell cycle progression in hepatocytes; role of inhibition at the level of mTOR/p70S6K. Br J Pharmacol. 2011 Apr;162(8):1781-91.
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