celastrol   Click here for help

GtoPdb Ligand ID: 10386

Synonyms: compound 2 [PMID: 28621943]
PDB Ligand Immunopharmacology Ligand
Compound class: Natural product
Comment: Celastrol is a plant-derived (from Tripterygium wilfordi, the Thunder god vine) natural product that has antioxidant, anti-inflammatory [1,8] and anti-obesity effects [5]. It has been reported as an inhibitor of RGS17 [3].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 1
Topological polar surface area 74.6
Molecular weight 450.28
XLogP 7.98
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES O=C1C=C2C(=CC=C3C2(C)CCC2(C3(C)CCC3(C2CC(C)(CC3)C(=O)O)C)C)C(=C1O)C
Isomeric SMILES O=C1C=C2C(=CC=C3[C@@]2(C)CC[C@@]2([C@]3(C)CC[C@@]3([C@H]2C[C@@](C)(CC3)C(=O)O)C)C)C(=C1O)C
InChI 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
InChI Key KQJSQWZMSAGSHN-JJWQIEBTSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Allison AC, Cacabelos R, Lombardi VR, Alvarez XA, Vigo C. (2001)
Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease.
Prog Neuropsychopharmacol Biol Psychiatry, 25 (7): 1341-57. [PMID:11513350]
2. Bodle CR, Mackie DI, Hayes MP, Schamp JH, Miller MR, Henry MD, Doorn JA, Houtman JCD, James MA, Roman DL. (2017)
Natural Products Discovered in a High-Throughput Screen Identified as Inhibitors of RGS17 and as Cytostatic and Cytotoxic Agents for Lung and Prostate Cancer Cell Lines.
J Nat Prod, 80 (7): 1992-2000. [PMID:28621943]
3. Bodle CR, Schamp JH, O'Brien JB, Hayes MP, Wu M, Doorn JA, Roman DL. (2018)
Screen Targeting Lung and Prostate Cancer Oncogene Identifies Novel Inhibitors of RGS17 and Problematic Chemical Substructures.
SLAS Discov, 23 (4): 363-374. [PMID:29351497]
4. Feng X, Guan D, Auen T, Choi JW, Salazar Hernández MA, Lee J, Chun H, Faruk F, Kaplun E, Herbert Z et al.. (2019)
IL1R1 is required for celastrol's leptin-sensitization and antiobesity effects.
Nat Med, 25 (4): 575-582. [PMID:30833749]
5. Pfuhlmann K, Schriever SC, Baumann P, Kabra DG, Harrison L, Mazibuko-Mbeje SE, Contreras RE, Kyriakou E, Simonds SE, Tiganis T et al.. (2018)
Celastrol-Induced Weight Loss Is Driven by Hypophagia and Independent From UCP1.
Diabetes, 67 (11): 2456-2465. [PMID:30158241]
6. Shi K, Chen X, Xie B, Yang SS, Liu D, Dai G, Chen Q. (2018)
Celastrol Alleviates Chronic Obstructive Pulmonary Disease by Inhibiting Cellular Inflammation Induced by Cigarette Smoke via the Ednrb/Kng1 Signaling Pathway.
Front Pharmacol, 9: 1276. [PMID:30498444]
7. Venkatesha SH, Moudgil KD. (2019)
Celastrol suppresses experimental autoimmune encephalomyelitis via MAPK/SGK1-regulated mediators of autoimmune pathology.
Inflamm Res, 68 (4): 285-296. [PMID:30820608]
8. Wong VKW, Qiu C, Xu SW, Law BYK, Zeng W, Wang H, Michelangeli F, Dias IRSR, Qu YQ, Chan TW et al.. (2019)
Ca2+ signalling plays a role in celastrol-mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in rats.
Br J Pharmacol, 176 (16): 2922-2944. [PMID:31124139]
9. Zhan X, Yan C, Chen Y, Wei X, Xiao J, Deng L, Yang Y, Qiu P, Chen Q. (2018)
Celastrol antagonizes high glucose-evoked podocyte injury, inflammation and insulin resistance by restoring the HO-1-mediated autophagy pathway.
Mol Immunol, 104: 61-68. [PMID:30439604]
10. Zhang J, Zhou K, Zhang X, Zhou Y, Li Z, Shang F. (2019)
Celastrol Ameliorates Inflammation in Human Retinal Pigment Epithelial Cells by Suppressing NF-κB Signaling.
J Ocul Pharmacol Ther, 35 (2): 116-123. [PMID:30596540]
11. Zhou X, Cao X, Tu H, Zhang ZR, Deng L. (2019)
Inflammation-Targeted Delivery of Celastrol via Neutrophil Membrane-Coated Nanoparticles in the Management of Acute Pancreatitis.
Mol Pharm, 16 (3): 1397-1405. [PMID:30753778]