Natural Product (NP) Details

General Information of the NP (ID: NP4353)
Name
Gamabufotalin
Synonyms
Gamabufotalin; 465-11-2; Gamabufogenin; Gamabufagin; Gammabufotalin; UNII-5HH3KM165O; 5HH3KM165O; CHEBI:80826; 5-[(3S,5R,8R,9S,10S,11R,13R,14S,17R)-3,11,14-trihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pyran-2-one; Gamabufalin; NSC 90384; SCHEMBL866038; CHEMBL465318; DTXSID40878664; 3-beta,11-alpha,14-Trihydroxy-5-beta-bufa-20,22-dienolide; HY-N0883; NSC90384; ZINC4916495; 3689AH; MFCD01740822; NSC-90384; AKOS030526148; CS-3701; NCGC00485918-01; C16962; 465G112; A827057; Q-100490; Q27149869; 5.beta.-Bufa-20, 3.beta.,11.alpha.,14-trihydroxy-; 5-beta-BUFA-20,22-DIENOLIDE, 3-beta,11-alpha,14-TRIHYDROXY-; 5beta-Bufa-20,22-dienolide, 3beta,11alpha,14-trihydroxy- (8CI); Bufa-20, 3,11,14-trihydroxy-, (3.beta.,5.beta.,11.alpha.)-; Bufa-20,22-dienolide, 3,11,14-trihydroxy-, (3-beta,5-beta,11-alpha)- (9CI); 5-[(3S,5R,8R,9S,10S,11R,13R,14S,17R)-10,13-dimethyl-3,11,14-tris(oxidanyl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pyran-2-one; 5-[(3S,5R,8R,9S,10S,11R,13R,14S,17R)-3,11,14-trihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2-pyranone
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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 Osteosarcoma [ICD-11: 2B51] Investigative [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.697
 
MDCK Permeability
 -5.233
 
PAMPA
 ++
 
HIA
 - - -
 
Distribution
VDss
 -0.322
 
PPB
 86.8%
 
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
 12.539
 
T1/2
 1.99
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
C24H34O5
PubChem CID
259803
Canonical SMILES
CC12CCC(CC1CCC3C2C(CC4(C3(CCC4C5=COC(=O)C=C5)O)C)O)O
InChI
1S/C24H34O5/c1-22-9-7-16(25)11-15(22)4-5-18-21(22)19(26)12-23(2)17(8-10-24(18,23)28)14-3-6-20(27)29-13-14/h3,6,13,15-19,21,25-26,28H,4-5,7-12H2,1-2H3/t15-,16+,17-,18-,19-,21-,22+,23-,24+/m1/s1
InChIKey
FMTLOAVOGWSPEF-KJRPADTMSA-N
CAS Number
CAS 465-11-2
ChEBI ID
CHEBI:80826
Herb ID
HBIN027073
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Arsenite      Prostate 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 BIRC5  Molecule Info 
Pathway MAP
Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation p38 beta  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
U-251MG CVCL_0021 Astrocytoma Homo sapiens
                    Experimental
                    Result(s)		 G2/M arrest, necrosis and autophagy appeared to cooperatively contribute to the synergistic cytotoxicity of AsIII and gamabufotalin.
Target and Pathway
Target(s) Aquaporin-4 (AQP4)  Molecule Info  [3]
Sodium pump subunit alpha-3 (ATP1A3)  Molecule Info  [3]
References
Reference 1 Gamabufotalin suppressed osteosarcoma stem cells through the TGF-Beta/periostin/PI3K/AKT pathway. Chem Biol Interact. 2020 Nov 1;331:109275.
Reference 2 Cytotoxic Effects of Arsenite in Combination With Gamabufotalin Against Human Glioblastoma Cell Lines. Front Oncol. 2021 Mar 16;11:628914.
Reference 3 Gamabufotalin induces a negative feedback loop connecting ATP1A3 expression and the AQP4 pathway to promote temozolomide sensitivity in glioblastoma cells by targeting the amino acid Thr794. Cell Prolif. 2020 Jan;53(1):e12732.
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