Natural Product (NP) Details

General Information of the NP (ID: NP1549)
Name
Naringenin
Synonyms
5,7-Dihydroxy-2-(4-hydroxyphenyl)chroman-4-one; 67604-48-2; 4',5,7-Trihydroxyflavanone; Naringenine; (+/-)-Naringenin; naringetol; 480-41-1; salipurpol; (-)-Naringenin; NARIGENIN; Salipurol; 5,7,4'-Trihydroxyflavanone; 93602-28-9; (S)-Naringenin; BE-14348A; NSC 34875; ( inverted exclamation markA)-Naringenin; CHEMBL32571; MLS000738094; MLS000028739; CHEBI:50202; Flavanone, 4',5,7-trihydroxy-; FTVWIRXFELQLPI-UHFFFAOYSA-N; NSC34875; NSC11855; MFCD00006844; SMR000059039; AK122638; NSC 11855; 4',7-Trihydroxyflavanone
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Species Origin Potentilla discolor ...     Click to Show/Hide
Potentilla discolor
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Rosales
Family: Rosaceae
Genus: Potentilla
Species: Potentilla discolor
Disease Hepatitis C virus infection [ICD-11: 1E51] Phase 1 [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.987
 
MDCK Permeability
 -4.762
 
PAMPA
 - -
 
HIA
 - - -
 
Distribution
VDss
 -0.011
 
PPB
 95%
 
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
 6.894
 
T1/2
 1.312
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
C15H12O5
PubChem CID
932
Canonical SMILES
C1C(OC2=CC(=CC(=C2C1=O)O)O)C3=CC=C(C=C3)O
InChI
1S/C15H12O5/c16-9-3-1-8(2-4-9)13-7-12(19)15-11(18)5-10(17)6-14(15)20-13/h1-6,13,16-18H,7H2
InChIKey
FTVWIRXFELQLPI-UHFFFAOYSA-N
CAS Number
CAS 67604-48-2
Herb ID
HBIN036366
ETMC ID
139
SymMap ID
SMIT00202
TCMSP ID
MOL004328
TTD Drug ID
D02ABO
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          ABT-737      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 [2]
                    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 Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model SGC-7901 CVCL_0520 Human gastric cancer Homo sapiens
                    Experimental
                    Result(s)		 ABT-737 in combination with naringenin showed enhanced anticancer effects on gastric cancer cells.
Target and Pathway
Target(s) Aromatase (CYP19A1)  Molecule Info  [3]
Cytochrome P450 1B1 (CYP1B1)  Molecule Info  [4]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)  Molecule Info  [5]
Lactoylglutathione lyase (GLO1)  Molecule Info  [6]
Oestrogen receptor beta (ESR2)  Molecule Info  [7]
BioCyc Superpathway of steroid hormone biosynthesis Click to Show/Hide
2 Estradiol biosynthesis II
3 Estradiol biosynthesis I
4 Superpathway of tryptophan utilization
5 Superpathway of melatonin degradation
6 Melatonin degradation I
7 Methylglyoxal degradation I
KEGG Pathway Steroid hormone biosynthesis Click to Show/Hide
2 Metabolic pathways
3 Ovarian steroidogenesis
4 Tryptophan metabolism
5 Metabolism of xenobiotics by cytochrome P450
6 Chemical carcinogenesis
7 MicroRNAs in cancer
8 Estrogen signaling pathway
9 Prolactin signaling pathway
10 Pyruvate metabolism
NetPath Pathway FSH Signaling Pathway Click to Show/Hide
2 TSH Signaling Pathway
3 IL4 Signaling Pathway
4 TGF_beta_Receptor Signaling Pathway
5 TCR Signaling Pathway
Panther Pathway Androgen/estrogene/progesterone biosynthesis Click to Show/Hide
Pathwhiz Pathway Androgen and Estrogen Metabolism Click to Show/Hide
2 Pyruvaldehyde Degradation
3 Pyruvate Metabolism
Pathway Interaction Database Plasma membrane estrogen receptor signaling Click to Show/Hide
2 Validated nuclear estrogen receptor beta network
3 Validated nuclear estrogen receptor alpha network
Reactome Endogenous sterols Click to Show/Hide
2 The canonical retinoid cycle in rods (twilight vision)
3 Nuclear Receptor transcription pathway
4 Pyruvate metabolism
WikiPathways Metapathway biotransformation Click to Show/Hide
2 Tryptophan metabolism
3 Oxidation by Cytochrome P450
4 Ovarian Infertility Genes
5 Metabolism of steroid hormones and vitamin D
6 FSH signaling pathway
7 Integrated Breast Cancer Pathway
8 Phase 1 - Functionalization of compounds
9 Estrogen metabolism
10 Benzo(a)pyrene metabolism
11 Tamoxifen metabolism
12 Nuclear Receptors Meta-Pathway
13 Estrogen Receptor Pathway
14 Sulindac Metabolic Pathway
15 Arylhydrocarbon receptor (AhR) signaling pathway
16 miR-targeted genes in muscle cell - TarBase
17 miR-targeted genes in lymphocytes - TarBase
18 miR-targeted genes in epithelium - TarBase
19 miR-targeted genes in adipocytes - TarBase
20 Steroid Biosynthesis
21 Prostate Cancer
22 SIDS Susceptibility Pathways
23 Integrated Pancreatic Cancer Pathway
24 Nuclear Receptors
References
Reference 1 ClinicalTrials.gov (NCT01091077) A Pilot Study of the Grapefruit Flavonoid Naringenin for HCV Infection
Reference 2 Enhanced anticancer effect of ABT-737 in combination with naringenin on gastric cancer cells. Exp Ther Med. 2016 Feb;11(2):669-673.
Reference 3 Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
Reference 4 Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorg Med Chem. 2010 Sep 1;18(17):6310-5.
Reference 5 Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries. J Med Chem. 2008 Jul 24;51(14):4188-99.
Reference 6 Structure-activity relationship of human GLO I inhibitory natural flavonoids and their growth inhibitory effects. Bioorg Med Chem. 2008 Apr 1;16(7):3969-75.
Reference 7 Subtle side-chain modifications of the hop phytoestrogen 8-prenylnaringenin result in distinct agonist/antagonist activity profiles for estrogen re... J Med Chem. 2006 Dec 14;49(25):7357-65.
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