Natural Product (NP) Details

General Information of the NP (ID: NP9078)
Name
Cinobufotalin
Synonyms
Cinobufotalin; 1108-68-5; CINOBUFOTLIN; UNII-L0QBZ37386; L0QBZ37386; NSC-90326; Q63409230; (1R,2R,2aR,3aS,3bR,5aS,7S,9aR,9bS,11aR)-5a,7-dihydroxy-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1',2':6,7]indeno[1,7a-b]oxiren-2-yl acetate; NSC 90326; SCHEMBL643121; CHEMBL517341; AMY40640; HY-N0880; NSC90326; ZINC4916381; 3551AH; MFCD28396383; AKOS030526073; CS-3698; 5-beta-Bufa-20,22-dienolide, 14,15-beta-epoxy-3-beta,5,16-beta-trihydroxy-, 16-acetate; 5.beta.-Bufa-20, 14,15.beta.-epoxy-3.beta.,5,16.beta.-trihydroxy-, 16-acetate; 5beta-Bufa-20,22-dienolide, 14,15beta-epoxy-3beta,5,16beta-trihydroxy-, 16-acetate (8CI); Bufa-20, 16-(acetyloxy)-14,15-epoxy-3,5-dihydroxy-, (3.beta.,5.beta.,15.beta.,16.beta.)-; Bufa-20,22-dienolide, 16-(acetyloxy)-14,15-epoxy-3,5-dihydroxy-, (3beta,5beta,15beta,16beta)- (9CI)
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Species Origin Andrias davidianus ...     Click to Show/Hide
Andrias davidianus
Kingdom: Metazoa
Phylum: Chordata
Class: Amphibia
Order: Caudata
Family: Cryptobranchidae
Genus: Andrias
Species: Andrias davidianus
Disease Lung cancer [ICD-11: 2C25] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.369
 
MDCK Permeability
 -4.981
 
PAMPA
 +++
 
HIA
 - - -
 
Distribution
VDss
 -0.263
 
PPB
 73.1%
 
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
 7.149
 
T1/2
 2.066
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
C26H34O7
PubChem CID
259776
Canonical SMILES
CC(=O)OC1C(C2(CCC3C(C24C1O4)CCC5(C3(CCC(C5)O)C)O)C)C6=COC(=O)C=C6
InChI
1S/C26H34O7/c1-14(27)32-21-20(15-4-5-19(29)31-13-15)24(3)10-7-17-18(26(24)22(21)33-26)8-11-25(30)12-16(28)6-9-23(17,25)2/h4-5,13,16-18,20-22,28,30H,6-12H2,1-3H3/t16-,17-,18+,20-,21+,22+,23+,24+,25-,26+/m0/s1
InChIKey
KBKUJJFDSHBPPA-ZNCGZLKOSA-N
CAS Number
CAS 1108-68-5
Herb ID
HBIN020703
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Cisplatin + 5-fluorouracil     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
                    In-vitro Model UM-SCC-5 CVCL_7762 Laryngeal squamous cell carcinoma Homo sapiens
FaDu CVCL_1218 Squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 TPF regimen combining cinobufotalin suppressed proliferation and promoted apoptosis synergistically in hypopharyngeal squamous cell carcinoma and laryngeal squamous cell carcinoma cells.
Target and Pathway
Target(s) ERK activator kinase 4 (MEK4)  Molecule Info  [3]
Forkhead box protein O1A (FOXO1)  Molecule Info  [4]
KEGG Pathway FoxO signaling pathway Click to Show/Hide
2 AMPK signaling pathway
3 Insulin signaling pathway
4 Thyroid hormone signaling pathway
5 Glucagon signaling pathway
6 Pathways in cancer
7 Transcriptional misregulation in cancer
8 Prostate cancer
NetPath Pathway IL2 Signaling Pathway Click to Show/Hide
2 TCR Signaling Pathway
Panther Pathway Insulin/IGF pathway-protein kinase B signaling cascade Click to Show/Hide
2 PI3 kinase pathway
3 CCKR signaling map ST
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling Click to Show/Hide
2 Signaling events mediated by HDAC Class III
3 Angiopoietin receptor Tie2-mediated signaling
4 CXCR4-mediated signaling events
5 FoxO family signaling
6 Regulation of Androgen receptor activity
7 IL6-mediated signaling events
8 Class I PI3K signaling events mediated by Akt
Reactome AKT phosphorylates targets in the nucleus Click to Show/Hide
2 Regulation of gene expression in beta cells
3 AKT-mediated inactivation of FOXO1A
4 Constitutive Signaling by AKT1 E17K in Cancer
5 MAPK6/MAPK4 signaling
WikiPathways ErbB Signaling Pathway Click to Show/Hide
2 Insulin Signaling
3 EGF/EGFR Signaling Pathway
4 Copper homeostasis
5 Pregnane X Receptor pathway
6 Endoderm Differentiation
7 Adipogenesis
8 AGE/RAGE pathway
9 B Cell Receptor Signaling Pathway
10 Signaling Pathways in Glioblastoma
11 FSH signaling pathway
12 Leptin signaling pathway
13 Integrated Breast Cancer Pathway
14 Regulation of beta-cell development
15 Androgen receptor signaling pathway
References
Reference 1 Pre-clinical evaluation of cinobufotalin as a potential anti-lung cancer agent. Biochem Biophys Res Commun. 2014 Sep 26;452(3):768-74.
Reference 2 Combination of TPF regimen and cinobufotalin inhibits proliferation and induces apoptosis in human hypopharyngeal and laryngeal squamous cell carcinoma cells. Onco Targets Ther. 2018 Dec 31;12:341-348.
Reference 3 Cinobufotalin powerfully reversed EBV-miR-BART22-induced cisplatin resistance via stimulating MAP2K4 to antagonize non-muscle myosin heavy chain IIA/glycogen synthase 3Beta/Beta-catenin signaling pathway. EBioMedicine. 2019 Oct;48:386-404.
Reference 4 Chemical compound cinobufotalin potently induces FOXO1-stimulated cisplatin sensitivity by antagonizing its binding partner MYH9. Signal Transduct Target Ther. 2019 Nov 18;4:48.
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