Natural Product (NP) Details

General Information of the NP (ID: NP6920)
Name
Guggulsterone
Synonyms
(Z)-Guggulsterone; Guggulsterone; Z-Guggulsterone; 39025-23-5; 95975-55-6; Guggulsterone E&Z; Guggulsterones Z; GUGGULSTERONE Z; Cis-Guggulsterone; UNII-6CST3U34GN; 6CST3U34GN; (Z)-Pregna-4,17(20)-diene-3,16-dione; (8R,9S,10R,13S,14S,17Z)-17-ethylidene-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthrene-3,16-dione; (17Z)-Pregna-4,17(20)-diene-3,16-dione; Gugulsterone; Pregna-4,17(20)-diene-3,16-dione; (8R,9S,10R,13S,14S,Z)-17-ethylidene-10,13-dimethyl-1,6,7,8,9,10,11,12,13,14,15,17-dodecahydro-3H-cyclopenta[a]phenanthrene-3,16(2H)-dione; Guggulsterone, (Z)-; Pregna-4,17(20)-diene-3,16-dione, (17Z)-; GS; (E&Z)-Guggulsterone; DSSTox_CID_13539; DSSTox_RID_79083; DSSTox_GSID_33539; SCHEMBL141657; CHEMBL410683; DTXSID1033539; BDBM21725; CHEBI:135338; BCP18087; Tox21_202518; MFCD01310757; AKOS015963432; ZINC118912814; (Z)-Guggulsterone, analytical standard; AC-6215; CCG-267610; NCGC00091910-01; NCGC00260067-01; AC-28813; (17Z)-pregna-4,17-diene-3,16-dione; 4,17(20)-trans-Pregnadiene-3,16-dione; CAS-39025-23-5; HY-107738; CS-0029421; S3792; V2228; (Z)-Guggulsterone, >=89% (HPLC), powder; 2-(2-Aminothiazol-3(2H)-yl)-1-phenylethanone; 975G556; BRD-K26674531-001-01-3; Q27264514; UNII-A4PW148END component WDXRGPWQVHZTQJ-OSJVMJFVSA-N; Guggulsterone Z, United States Pharmacopeia (USP) Reference Standard; (1S,2R,10R,11S,14Z,15S)-14-ethylidene-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-ene-5,13-dione
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Species Origin Commiphora mukul ...     Click to Show/Hide
Commiphora mukul
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Burseraceae
Genus: Commiphora
Species: Commiphora mukul
Disease Osteoarthritis [ICD-11: FA00-FA05] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.611
 
MDCK Permeability
 -4.717
 
PAMPA
 - - -
 
HIA
 - - -
 
Distribution
VDss
 -0.076
 
PPB
 97%
 
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
 10.774
 
T1/2
 0.369
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
C21H28O2
PubChem CID
6450278
Canonical SMILES
CC=C1C(=O)CC2C1(CCC3C2CCC4=CC(=O)CCC34C)C
InChI
1S/C21H28O2/c1-4-16-19(23)12-18-15-6-5-13-11-14(22)7-9-20(13,2)17(15)8-10-21(16,18)3/h4,11,15,17-18H,5-10,12H2,1-3H3/b16-4+/t15-,17+,18+,20+,21-/m1/s1
InChIKey
WDXRGPWQVHZTQJ-OSJVMJFVSA-N
CAS Number
CAS 39025-23-5
ChEBI ID
CHEBI:135338
Herb ID
HBIN028535
SymMap ID
SMIT03635
TCMSP ID
MOL001175
TTD Drug ID
D0G8BV
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Gemcitabine      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 AKT1  Molecule Info 
Pathway MAP
                    In-vitro Model MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model To ceate the subcutaneous xenograft model, mice were subcutaneously inoculated with MiaPaCa-2 cells (1*106cells/mouse) in 1 mL of Matrigel.
                    Experimental
                    Result(s)		 The combination of guggulsterone to gemcitabine enhanced antitumor efficacy through apoptosis induction by suppressing Akt and nuclear factor KappaB activity and by modulating apoptosis-related protein expression in pancreatic cancer.
Target and Pathway
Target(s) Farnesoid X-activated receptor (FXR)  Molecule Info  [3]
KEGG Pathway Bile secretion Click to Show/Hide
Pathway Interaction Database RXR and RAR heterodimerization with other nuclear receptor Click to Show/Hide
Reactome Recycling of bile acids and salts Click to Show/Hide
2 PPARA activates gene expression
3 Endogenous sterols
WikiPathways Nuclear Receptors in Lipid Metabolism and Toxicity Click to Show/Hide
2 Nuclear Receptors Meta-Pathway
3 Farnesoid X Receptor Pathway
4 Drug Induction of Bile Acid Pathway
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2745).
Reference 2 Enhanced antitumor effect of combination therapy with gemcitabine and guggulsterone in pancreatic cancer. Pancreas. 2012 Oct;41(7):1048-57.
Reference 3 Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia. J Nat Prod. 2009 Jan;72(1):24-8.
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