Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C21H28O2 |
| Molecular Weight | 312.4458 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12CC(=O)\C(=C\C)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CCC4=CC(=O)CC[C@]34C
InChI
InChIKey=WDXRGPWQVHZTQJ-AUKWTSKRSA-N
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
| Molecular Formula | C21H28O2 |
| Molecular Weight | 312.4458 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 1 |
| Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/16250653https://www.ncbi.nlm.nih.gov/pubmed/11988537 | https://www.ncbi.nlm.nih.gov/pubmed/12089353Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/26337021 | https://www.ncbi.nlm.nih.gov/pubmed/17292610 | https://www.ncbi.nlm.nih.gov/pubmed/23688559 | https://www.ncbi.nlm.nih.gov/pubmed/26879835
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16250653https://www.ncbi.nlm.nih.gov/pubmed/11988537 | https://www.ncbi.nlm.nih.gov/pubmed/12089353
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/26337021 | https://www.ncbi.nlm.nih.gov/pubmed/17292610 | https://www.ncbi.nlm.nih.gov/pubmed/23688559 | https://www.ncbi.nlm.nih.gov/pubmed/26879835
Guggulsterone is a naturally occuring bioactive plant sterol isolated from the gum resin of guggul (Commiphora wightii), which potently reverses multi-drug resistance in a number of human cancer cell lines, extending the efficacy of chemotherapy. Guggulsterone is a highly efficacious antagonist of the farnesoid X receptor (FXR), a nuclear hormone receptor that is activated by bile acids. Z-guggulsterone and E-guggulsterone were identified as the key active ingredients responsible for the hypolipidemic activity of guggulipid. Both isomers possess similar hypolipidemic activity and mixture of the Z- and E-isomers (80:20) has been shown to lower cholesterol and triglycerides in normal and high-fat-fed rats.
Originator
Sources: http://www.sciencedirect.com/science/article/pii/S004040200193577X?via%3Dihubhttps://www.ncbi.nlm.nih.gov/pubmed/12089353
Curator's Comment: The laboratory of the Dr. Sukh Dev the first isolated of Z- and E-guggulsterones from guggulipid in 1971.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: Q96RI1 Gene ID: 9971.0 Gene Symbol: NR1H4 Target Organism: Homo sapiens (Human) |
|||
Target ID: CHEMBL2047 |
12.0 nM [IC50] | ||
Target ID: CHEMBL1871 |
660.0 nM [EC50] | ||
Target ID: CHEMBL2034 |
6060.0 nM [IC50] | ||
Target ID: CHEMBL1994 |
1880.0 nM [IC50] | ||
Target ID: CHEMBL3401 |
2.4 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. | 2002 Jul |
|
| A natural product that lowers cholesterol as an antagonist ligand for FXR. | 2002 May 31 |
|
| Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7alpha-hydroxylase gene. | 2003 Apr 25 |
|
| Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. | 2003 Mar 21 |
|
| Guggulsterone activates multiple nuclear receptors and induces CYP3A gene expression through the pregnane X receptor. | 2004 Aug |
|
| Megalin and cubilin expression in gallbladder epithelium and regulation by bile acids. | 2004 Dec |
|
| Guggulsterone inhibits NF-kappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis. | 2004 Nov 5 |
|
| The ratio of constitutive androstane receptor to pregnane X receptor determines the activity of guggulsterone against the Cyp2b10 promoter. | 2005 Jul |
|
| Enhanced effects of guggulsterone plus 1,25(OH)2D3 on 3T3-L1 adipocytes. | 2007 Dec 21 |
|
| Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products. | 2007 Jun 30 |
|
| Enhanced steatosis by nuclear receptor ligands: a study in cultured human hepatocytes and hepatoma cells with a characterized nuclear receptor expression profile. | 2010 Mar 30 |
|
| Regulation of human carbonyl reductase 3 (CBR3; SDR21C2) expression by Nrf2 in cultured cancer cells. | 2010 Oct 5 |
|
| Discovery of sulfated sterols from marine invertebrates as a new class of marine natural antagonists of farnesoid-X-receptor. | 2011 Mar 10 |
|
| Identification of UV-protective activators of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) by combining a chemical library screen with computer-based virtual screening. | 2012 Sep 21 |
|
| Expression of DNA methyltransferases in breast cancer patients and to analyze the effect of natural compounds on DNA methyltransferases and associated proteins. | 2013 Mar |
|
| Suppression of the pregnane X receptor during endoplasmic reticulum stress is achieved by down-regulating hepatocyte nuclear factor-4α and up-regulating liver-enriched inhibitory protein. | 2015 Apr |
|
| Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis. | 2015 Mar 15 |
Patents
Sample Use Guides
in experimental animals: Serum lipids were found to be lowered by Guggulsterone (an 80:20 mixture of the Z- and E-isomers) (50 mgkg, b.w.) in triton WR-1339 induced hyperlipaemia. Chronic feeding of this drug (5 mg/kg, b.w.) in animals simultaneously fed with cholesterol (25 m%kg, b.w.) for 30 days, caused lowering in the lipid and apoprotein levels of very low density and low density lipoproteins in experimental animals.
Route of Administration:
Oral
| Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 19:43:12 GMT 2023
by
admin
on
Fri Dec 15 19:43:12 GMT 2023
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| Record UNII |
9B259YE66O
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| Record Status |
Validated (UNII)
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| Record Version |
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2405 (Number of products:11)
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39025-24-6
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m5878
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