CELASTROL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H38O4
Molecular Weight	450.6096
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C[C@@](C)(CC[C@]1(C)CC[C@]3(C)C4=CC=C5C(C)=C(O)C(=O)C=C5[C@]4(C)CC[C@@]23C)C(O)=O

InChI

InChIKey=KQJSQWZMSAGSHN-JJWQIEBTSA-N

InChI=1S/C29H38O4/c1-17-18-7-8-21-27(4,19(18)15-20(30)23(17)31)12-14-29(6)22-16-26(3,24(32)33)10-9-25(22,2)11-13-28(21,29)5/h7-8,15,22,31H,9-14,16H2,1-6H3,(H,32,33)/t22-,25-,26-,27+,28-,29+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C29H38O4
Molecular Weight	450.6096
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11513350
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10072949 | https://www.ncbi.nlm.nih.gov/pubmed/26000480

Celastrol is a pentacyclic triterpenoid isolated from the root extracts of Tripterygium wilfordii, a perrennial creeping plant indigenous to large area in Southern China. Celastrol possess antioxidant and anti-inflammatory and anticancer action. In the mouse model of rheumatoid arthritis it reduced inflammatory swelling, suppressed humoral and skin response and reduced pathological progression of joint. Celastrol demonstrated efficacy in transgenic mouse model of amyotrophic lateral sclerosis. Anticancer activity of celastrol was shown in xenograft models of prostate cancer. Celastrol suppresses food intake, blocks reduction of energy expenditure, and leads to up to 45% weight loss in hyperleptinemic diet-induced obese (DIO) mice by increasing leptin sensitivity. Celastrol acts by interfering with the activity of Hsp90, IKK-beta and proteasome S26 subunit.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Heat shock protein HSP90 35 Target ID: CHEMBL2095165 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19858214	Inhibitor 8297
Inhibitor of nuclear factor kappa-B kinase subunit beta 5 Target ID: O14920 Gene ID: 3551.0 Gene Symbol: IKBKB Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27931154 \| https://www.ncbi.nlm.nih.gov/pubmed/16984800	Inhibitor 8297
26S proteosome 7 Target ID: CHEMBL2364701 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16651429	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10072949	Primary	Preclinical	Unknown Approved Use Unknown
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14519971 https://www.ncbi.nlm.nih.gov/pubmed/16651429	Primary	Preclinical	Unknown Approved Use Unknown
Amyotrophic lateral sclerosis 41 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16909005	Primary	Preclinical	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24214023	Primary	Basic research	Unknown Approved Use Unknown
Obesity 203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26000480	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Tripterine inhibits the expression of adhesion molecules in activated endothelial cells.	2006 Aug	16769766
Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators.	2006 Oct	17010675
Calpain-mediated androgen receptor breakdown in apoptotic prostate cancer cells.	2008 Dec	18726991
Pharmacogenomic approach reveals a role for the x(c)- cystine/glutamate antiporter in growth and celastrol resistance of glioma cell lines.	2010 Mar	20007406
Up-regulation of death receptor 4 and 5 by celastrol enhances the anti-cancer activity of TRAIL/Apo-2L.	2010 Nov 28	20605676
Celastrol induces apoptosis in non-small-cell lung cancer A549 cells through activation of mitochondria- and Fas/FasL-mediated pathways.	2011 Aug	21466843
Celastrol inhibits Tat-mediated human immunodeficiency virus (HIV) transcription and replication.	2011 Jul 29	21763500
A critical role for MAPK signalling pathways in the transcriptional regulation of toll like receptors.	2013	23405061
Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells.	2013 Oct	23942037
Celastrol prevents cadmium-induced neuronal cell death via targeting JNK and PTEN-Akt/mTOR network.	2014 Jan	24111524
Celastrol ameliorates murine colitis via modulating oxidative stress, inflammatory cytokines and intestinal homeostasis.	2014 Mar 5	24384223
Accumulation of heme oxygenase-1 (HSP32) in Xenopus laevis A6 kidney epithelial cells treated with sodium arsenite, cadmium chloride or proteasomal inhibitors.	2014 Nov	25064141
The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells.	2015 Jan 16	25477506
Direct inhibition of c-Myc-Max heterodimers by celastrol and celastrol-inspired triterpenoids.	2015 Oct 20	26474287

Patents

Sample Use Guides

In Vivo Use Guide

In collagen-induced arthritis study on mice, celastrol was administered orally at 15 and 30 mg/kg. In model of prostate cancer celastrol was administered at doses 1-3 mg/kg intraperitoneally.

Route of Administration: Other

In Vitro Use Guide

The ability of celastrol to inhibit NF-kB activation was studied in vitro in Jurkat cell line. Cells were preincubated with various concentrations of celastrol for 30 min prior to stimulation with TNF-alpha or PMA. After the stimulation, nuclear extracts were prepared and DNA-binding activity of NF-kB in the nuclear extracts was measured by electrophoretic mobility shift assays. Pretreatment of celastrol dose-dependently inhibited DNA-binding activity of NF-kB induced by TNF-a or PMA. The effect was apparent at concentrations of celastrol below 0.3 ug/ml.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:54:18 UTC 2023` Edited by `admin` on `Sat Dec 16 09:54:18 UTC 2023`
Record UNII	L8GG98663L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CELASTROL

Common Name

English

24,25,26-TRINOROLEANA-1(10),3,5,7-TETRAEN-29-OIC ACID, 3-HYDROXY-9,13-DIMETHYL-2-OXO-, (9.BETA.,13.ALPHA.,14.BETA.,20.ALPHA.)-

Common Name

English

NSC-70931

Code

English

TRIPTERIN

Common Name

English

CELASTROL [MI]

Common Name

English

24-NOR-D:A-FRIEDOOLEANA-1(10),3,5,7-TETRAEN-29-OIC ACID, 3-HYDROXY-2-OXO-

Common Name

English

Code System Code Type Description

NSC

70931