Natural Product (NP) Details

General Information of the NP (ID: NP8829)
Name
Oroxylin A
Synonyms
Oroxylin; 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; 5,7-dihydroxy-6-methoxy-2-phenyl-4H-1-benzopyran-4-one; 4H-1-Benzopyran-4-one, 5,7-dihydroxy-6-methoxy-2-phenyl-; UNII-53K24Z586G; Baicalein 6-methyl ether;6-Methoxybaicalein; CHEBI:61668; 5,7-dihydroxy-6-methoxy-2-phenyl-4H-chromen-4-one; MFCD02259441; 53K24Z586G; Oroxylin-A; 6-Methoxybaicalein;; baicalein 6-methyl ether; Oroxylin?A; 5,7-dihydroxy-6-methoxyflavone; 5,7-Dihydroxy-6-methoxyflavone;; SCHEMBL431423; CHEMBL183513; DTXSID70197375; Oroxylin A, >=98% (HPLC); BCP31803; EX-A4028; HY-N0560; ZINC5998558; BDBM50430091; LMPK12111096; s9204; AKOS015903364; CCG-267292; CS-4948; AC-31960; AK168138; BS-16891; FT-0688332; O-160; Y0150; A14367; 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one.; 5,7-Dihydroxy-6-methoxy-2-phenyl-chromen-4-one; Q3356627
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Species Origin Oroxylum indicum ...     Click to Show/Hide
Oroxylum indicum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Lamiales
Family: Bignoniaceae
Genus: Oroxylum
Species: Oroxylum indicum
Disease Ovarian cancer [ICD-11: 2C73] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.891
 
MDCK Permeability
 -4.733
 
PAMPA
 - - -
 
HIA
 - - -
 
Distribution
VDss
 -0.618
 
PPB
 98.8%
 
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
 4.134
 
T1/2
 0.985
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
C16H12O5
PubChem CID
5320315
Canonical SMILES
COC1=C(C2=C(C=C1O)OC(=CC2=O)C3=CC=CC=C3)O
InChI
1S/C16H12O5/c1-20-16-11(18)8-13-14(15(16)19)10(17)7-12(21-13)9-5-3-2-4-6-9/h2-8,18-19H,1H3
InChIKey
LKOJGSWUMISDOF-UHFFFAOYSA-N
CAS Number
CAS 480-11-5
Herb ID
HBIN038302
ETMC ID
1498
SymMap ID
SMIT18852
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		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    In-vivo Model Murine hepatoma 22 (H22) cells were diluted with icy 0.9% saline and inoculated subcutaneously at right axilla of mice (5*106 viable cells/mL).
                    Experimental
                    Result(s)		 The anti-hepatocellular carcinoma effects in vitro and in vivo of 5-FU and oroxylin A combinations were synergistic and oroxylin A increased the sensitivity of HepG2 cells to 5-FU by modulating the metabolic enzymes of 5-FU and apoptotic-related proteins.
    β. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Cisplatin      Bladder cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     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 XPC  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
PLA-801D CVCL_7110 Lung giant cell carcinoma Homo sapiens
PC-9 CVCL_B260 Lung adenocarcinoma Homo sapiens
HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Oroxylin A reverses hypoxia-induced cisplatin resistance through inhibiting HIF-1alpha mediated XPC transcription.
Target and Pathway
Target(s) Apoptosis regulator Bcl-2 (BCL-2)  Molecule Info  [4]
Caspase-3 (CASP3)  Molecule Info  [5]
Cyclin-dependent kinase 7 (CDK7)  Molecule Info  [6]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 p53 signaling pathway
3 Apoptosis
4 Natural killer cell mediated cytotoxicity
5 TNF signaling pathway
6 Serotonergic synapse
7 Non-alcoholic fatty liver disease (NAFLD)
8 Alzheimer's disease
9 Parkinson's disease
10 Amyotrophic lateral sclerosis (ALS)
11 Huntington's disease
12 Epithelial cell signaling in Helicobacter pylori infection
13 Pertussis
14 Legionellosis
15 Toxoplasmosis
16 Amoebiasis
17 Tuberculosis
18 Hepatitis B
19 Herpes simplex infection
20 Pathways in cancer
21 Viral carcinogenesis
22 Proteoglycans in cancer
23 MicroRNAs in cancer
24 Colorectal cancer
25 Viral myocarditis
26 NF-kappa B signaling pathway
27 HIF-1 signaling pathway
28 Sphingolipid signaling pathway
29 Protein processing in endoplasmic reticulum
30 PI3K-Akt signaling pathway
31 Adrenergic signaling in cardiomyocytes
32 Focal adhesion
33 Neurotrophin signaling pathway
34 Cholinergic synapse
35 Epstein-Barr virus infection
36 Prostate cancer
37 Small cell lung cancer
38 Basal transcription factors
39 Nucleotide excision repair
40 Cell cycle
NetPath Pathway TCR Signaling Pathway Click to Show/Hide
2 IL2 Signaling Pathway
3 IL4 Signaling Pathway
4 IL5 Signaling Pathway
5 IL3 Signaling Pathway
6 Leptin Signaling Pathway
7 RANKL Signaling Pathway
8 TSLP Signaling Pathway
Panther Pathway Apoptosis signaling pathway Click to Show/Hide
2 FAS signaling pathway
3 Huntington disease
4 CCKR signaling map ST
5 Oxidative stress response
Pathway Interaction Database LPA receptor mediated events Click to Show/Hide
2 Calcineurin-regulated NFAT-dependent transcription in lymphocytes
3 FAS (CD95) signaling pathway
4 Role of Calcineurin-dependent NFAT signaling in lymphocytes
5 Posttranslational regulation of adherens junction stability and dissassembly
6 p75(NTR)-mediated signaling
7 HIV-1 Nef: Negative effector of Fas and TNF-alpha
8 Caspase Cascade in Apoptosis
9 Syndecan-2-mediated signaling events
10 IL2-mediated signaling events
11 IL2 signaling events mediated by PI3K
12 Ceramide signaling pathway
13 Direct p53 effectors
14 RXR and RAR heterodimerization with other nuclear receptor
15 ATF-2 transcription factor network
16 C-MYB transcription factor network
17 Signaling events mediated by Stem cell factor receptor (c-Kit)
18 EPO signaling pathway
19 IL2 signaling events mediated by STAT5
20 Validated targets of C-MYC transcriptional repression
21 Retinoic acid receptors-mediated signaling
Reactome SMAC binds to IAPs Click to Show/Hide
2 SMAC-mediated dissociation of IAP:caspase complexes
3 Apoptotic cleavage of cellular proteins
4 Degradation of the extracellular matrix
5 NADE modulates death signalling
6 Activation of DNA fragmentation factor
7 Caspase-mediated cleavage of cytoskeletal proteins
8 Activation of BAD and translocation to mitochondria
9 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
10 The NLRP1 inflammasome
11 NoRC negatively regulates rRNA expression
12 Formation of TC-NER Pre-Incision Complex
13 Dual incision in TC-NER
14 Gap-filling DNA repair synthesis and ligation in TC-NER
15 Cyclin E associated events during G1/S transition
16 Cyclin D associated events in G1
17 Cyclin A/B1 associated events during G2/M transition
18 Cyclin A:Cdk2-associated events at S phase entry
19 RNA Polymerase I Transcription Initiation
WikiPathways DNA Damage Response Click to Show/Hide
2 SIDS Susceptibility Pathways
3 Apoptosis Modulation by HSP70
4 MAPK Signaling Pathway
5 Copper homeostasis
6 FAS pathway and Stress induction of HSP regulation
7 Signaling by Hippo
8 Apoptosis
9 Amyotrophic lateral sclerosis (ALS)
10 Spinal Cord Injury
11 BDNF signaling pathway
12 Integrated Pancreatic Cancer Pathway
13 Oncostatin M Signaling Pathway
14 Parkinsons Disease Pathway
15 Corticotropin-releasing hormone
16 Allograft Rejection
17 AGE/RAGE pathway
18 TNF alpha Signaling Pathway
19 Prostate Cancer
20 Alzheimers Disease
21 TWEAK Signaling Pathway
22 Integrated Breast Cancer Pathway
23 Signalling by NGF
24 Integrated Cancer pathway
25 Regulation of Apoptosis
26 Intrinsic Pathway for Apoptosis
27 Apoptotic execution phase
28 Apoptosis Modulation and Signaling
29 miRNA Regulation of DNA Damage Response
30 DNA Damage Response (only ATM dependent)
31 Senescence and Autophagy in Cancer
32 IL-2 Signaling Pathway
33 Focal Adhesion
34 Kit receptor signaling pathway
35 IL-3 Signaling Pathway
36 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
37 Nanoparticle triggered autophagic cell death
38 Interleukin-11 Signaling Pathway
39 miR-targeted genes in muscle cell - TarBase
40 miR-targeted genes in lymphocytes - TarBase
41 miR-targeted genes in leukocytes - TarBase
42 TP53 Network
43 Influenza A virus infection
44 IL-5 Signaling Pathway
45 G1 to S cell cycle control
46 Eukaryotic Transcription Initiation
47 Cardiac Hypertrophic Response
48 S Phase
49 HIV Life Cycle
50 Nucleotide Excision Repair
51 RNA Polymerase II Transcription
52 RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription
53 mRNA Capping
54 Mitotic G2-G2/M phases
55 Mitotic G1-G1/S phases
56 MicroRNAs in cardiomyocyte hypertrophy
References
Reference 1 Oroxylin A exerts anticancer effects on human ovarian cancer cells via the PPARGamma dependent reversal of the progesterone receptor membrane component 1/2 expression profile. Oncol Rep. 2020 Apr;43(4):1309-1318.
Reference 2 Synergistic effect of 5-fluorouracil and the flavanoid oroxylin A on HepG2 human hepatocellular carcinoma and on H22 transplanted mice. Cancer Chemother Pharmacol. 2010 Feb;65(3):481-9.
Reference 3 Oroxylin A reverses hypoxia-induced cisplatin resistance through inhibiting HIF-1alpha mediated XPC transcription. Oncogene. 2020 Nov;39(45):6893-6905.
Reference 4 The role of Nrf2 and apoptotic signaling pathways in oroxylin A-mediated responses in HCT-116 colorectal adenocarcinoma cells and xenograft tumors. Anticancer Drugs. 2012 Jul;23(6):651-8.
Reference 5 Molecular Targets and Mechanisms of Scutellariae radix-Coptidis rhizoma Drug Pair for the Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking. Evid Based Complement Alternat Med. 2021 Jun 4;2021:9929093.
Reference 6 Oroxylin A induces G2/M phase cell-cycle arrest via inhibiting Cdk7-mediated expression of Cdc2/p34 in human gastric carcinoma BGC-823 cells. J Pharm Pharmacol. 2008 Nov;60(11):1459-63.
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