GUGGULSTERONE, (Z)-

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

Structure Search

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-OSJVMJFVSA-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

HIDE SMILES / InChI

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

Description
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

Approval Year

Targets

Primary Target	Pharmacology	Potency
Bile acid receptor 5 Target ID: Q96RI1 Gene ID: 9971.0 Gene Symbol: NR1H4 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11988537	Antagonist 2778
Bile acid receptor FXR 31 Target ID: CHEMBL2047 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26337021	Antagonist 2778	12.0 nM [IC50]
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16250653	Agonist 2678	660.0 nM [EC50]
Glucocorticoid receptor 172 Target ID: CHEMBL2034 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16250653	Antagonist 2778	6060.0 nM [IC50]
Mineralocorticoid receptor 53 Target ID: CHEMBL1994 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16250653	Antagonist 2778	1880.0 nM [IC50]
Pregnane X receptor 35 Target ID: CHEMBL3401 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23688559	Agonist 2678	2.4 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578
Unknown 2578

PubMed

Title	Date	PubMed
A natural product that lowers cholesterol as an antagonist ligand for FXR.	2002 May 31	11988537
Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump.	2003 Mar 21	12525500
Enhanced effects of guggulsterone plus 1,25(OH)2D3 on 3T3-L1 adipocytes.	2007 Dec 21	17959142
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	20079722
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	22851183
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	25616597
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	25655198

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

Z-guggulsterone attenuates iNOS protein induction in BV-2 cells exposed to LPS. Pretreatment of Z-guggulsterone (30 min) at different concentrations (1, 10, 30 mkM) inhibited iNOS protein expression in cells stimulated by LPS (1 mkg/mL).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:46:25 GMT 2023` Edited by `admin` on `Sat Dec 16 01:46:25 GMT 2023`
Record UNII	6CST3U34GN
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GUGGULSTERONE, (Z)-

Common Name

English

4,17(20)-CIS-PREGNADIENE-3,6-DIONE

Common Name

English

CIS-GUGGULSTERONE

Common Name

English

Z-GUGGULSTERONE

Common Name

English

PREGNA-4,17(20)-DIENE-3,16-DIONE, (17Z)-

Systematic Name

English

GUGGULSTERONE Z-FORM

Common Name

English

(17Z)-GUGGULSTERONE

Common Name

English

GUGGULSTERONE Z (CONSTITUENT OF GUGGUL) [DSC]

Common Name

English

GUGGULSTERONE Z-FORM [MI]

Common Name

English

GUGGULSTERONE Z

Common Name

English

GUGGULSTERONE Z [USP-RS]

Common Name

English

Classification Tree Code System Code

DSLD

2405 (Number of products:11)