GUGGULSTERONE, (E)-

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-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

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
The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor.	2002 Jul	12089353
A natural product that lowers cholesterol as an antagonist ligand for FXR.	2002 May 31	11988537
Guggulsterone inhibits NF-kappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis.	2004 Nov 5	15322087
The ratio of constitutive androstane receptor to pregnane X receptor determines the activity of guggulsterone against the Cyp2b10 promoter.	2005 Jul	15833898
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 `Fri Dec 15 19:43:12 UTC 2023` Edited by `admin` on `Fri Dec 15 19:43:12 UTC 2023`
Record UNII	9B259YE66O
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GUGGULSTERONE, (E)-

Common Name

English

(-)-(E)-GUGGULSTERONE

Common Name

English

E-GUGGULSTERONE

Common Name

English

4,17(20)-(TRANS)-PREGNADIENE-3,16-DIONE

Common Name

English

GUGGULSTERONE E-FORM [MI]

Common Name

English

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

Systematic Name

English

GUGGULSTERONE E (CONSTITUENT OF GUGGUL) [DSC]

Common Name

English

TRANS-GUGGULSTERONE

Common Name

English

GUGGULSTERONE E-FORM

Common Name

English

Classification Tree Code System Code

DSLD

2405 (Number of products:11)