Celastrol

Celastrol

Names
IUPAC name 3-Hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid
Other names Tripterine
Identifiers
CAS Number	34157-83-0
3D model (Jmol)	Interactive image
ChemSpider	109405
ECHA InfoCard	100.164.266
PubChem	122724
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 Key: KQJSQWZMSAGSHN-JJWQIEBTSA-N InChI=1/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 Key: KQJSQWZMSAGSHN-JJWQIEBTBS
SMILES CC1=C(C(=O)C=C2C1=CC=C3[C@]2(CC[C@@]4([C@@]3(CC[C@@]5([C@H]4C[C@](CC5)(C)C(=O)O)C)C)C)C)O
Properties
Chemical formula	C29H38O4
Molar mass	450.62 g·mol^−1
Appearance	Crystalline solid
Melting point	213 °C (415 °F; 486 K)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Celastrol (tripterine) is a chemical compound isolated from the root extracts of Tripterygium wilfordii (Thunder god vine) and Celastrus regelii. Celastrol is a pentacyclic triterpenoid and belongs to the family of quinone methides.

In in vitro and in vivo animal experiments, celastrol exhibits antioxidant,^[2] anti-inflammatory,^[3][4] anticancer,^[5][6][7][8] and insecticidal ^[9] activities. It has been shown to have obesity-controlling effects in mice.^[10] Celastrol has also shown to possess (by inhibition of NF-κB in the hypothalamus^[11]) anti-diabetic effects on diabetic nephropathy and improve whole-body insulin resistance^[12][13]

References

1. Ryu, Y. B.; Park, S. J.; Kim, Y. M.; Lee, J. Y.; Seo, W. D.; Chang, J. S.; Park, K. H.; Rho, M. C.; Lee, W. S. (2010). "SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii". Bioorganic & Medicinal Chemistry Letters. 20 (6): 1873. doi:10.1016/j.bmcl.2010.01.152.
2. Allison, A. C.; Cacabelos, R.; Lombardi, V. R. M.; Alvarez, X. A.; Vigo, C. (2001). "Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 25 (7): 1341–1357. doi:10.1016/S0278-5846(01)00192-0. PMID 11513350.
3. Kim, D. H.; Shin, E. K.; Kim, Y. H.; Lee, B. W.; Jun, J. -G.; Park, J. H. Y.; Kim, J. -K. (2009). "Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated from Celastrus regelii". European Journal of Clinical Investigation. 39 (9): 819–827. doi:10.1111/j.1365-2362.2009.02186.x. PMID 19549173.
4. Venkatesha, S. H.; Yu, H.; Rajaiah, R.; Tong, L.; Moudgil, K. D. (2011). "Celastrus-derived Celastrol Suppresses Autoimmune Arthritis by Modulating Antigen-induced Cellular and Humoral Effector Responses". Journal of Biological Chemistry. 286 (17): 15138–15146. doi:10.1074/jbc.M111.226365. PMC 3083183. PMID 21402700.
5. Lee, J. H.; Choi, K. J.; Seo, W. D.; Jang, S. Y.; Kim, M.; Lee, B. W.; Kim, J. Y.; Kang, S.; Park, K. H.; Lee, Y. S.; Bae, S. (2011). "Enhancement of radiation sensitivity in lung cancer cells by celastrol is mediated by inhibition of Hsp90". International Journal of Molecular Medicine. 27 (3). doi:10.3892/ijmm.2011.601. PMID 21249311.
6. Tiedemann, R. E.; Schmidt, J.; Keats, J. J.; Shi, C. -X.; Zhu, Y. X.; Palmer, S. E.; Mao, X.; Schimmer, A. D.; Stewart, A. K. (2008). "Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF- B with antimyeloma activity in vitro and in vivo". Blood. 113 (17): 4027–4037. doi:10.1182/blood-2008-09-179796. PMID 19096011.
7. Zhu, H.; Liu, X. -W.; Cai, T. -Y.; Cao, J.; Tu, C. -X.; Lu, W.; He, Q. -J.; Yang, B. (2010). "Celastrol Acts as a Potent Antimetastatic Agent Targeting 1 Integrin and Inhibiting Cell-Extracellular Matrix Adhesion, in Part via the p38 Mitogen-Activated Protein Kinase Pathway". Journal of Pharmacology and Experimental Therapeutics. 334 (2): 489–499. doi:10.1124/jpet.110.165654. PMID 20472666.
8. Byun, J. -Y.; Kim, M. -J.; Eum, D. -Y.; Yoon, C. -H.; Seo, W. -D.; Park, K. H.; Hyun, J. -W.; Lee, Y. -S.; Lee, J. -S.; Yoon, M. -Y.; Lee, S. -J. (2009). "Reactive Oxygen Species-Dependent Activation of Bax and Poly(ADP-ribose) Polymerase-1 is Required for Mitochondrial Cell Death Induced by Triterpenoid Pristimerin in Human Cervical Cancer Cells". Molecular Pharmacology. 76 (4): 734–744. doi:10.1124/mol.109.056259. PMID 19574249.
9. Avilla, J. S.; Teixidò, A.; Velázquez, C.; Alvarenga, N.; Ferro, E.; Canela, R. (2000). "Insecticidal Activity of Maytenus Species (Celastraceae) Nortriterpene Quinone Methides against Codling Moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae)". Journal of Agricultural and Food Chemistry. 48 (1): 88–92. doi:10.1021/jf990008w. PMID 10637057.
10. Liu, Junli; Lee, Jaemin; Salazar Hernandez, Mario Andres; Mazitschek, Ralph; Ozcan, Umut (May 2015). "Treatment of Obesity with Celastrol". Cell. 161 (5): 999–1011. doi:10.1016/j.cell.2015.05.011.
11. Lee, J. H., Koo, T. H., Yoon, H., Jung, H. S., Jin, H. Z., Lee, K., ... & Lee, J. J. (2006). Inhibition of NF-κB activation through targeting IκB kinase by celastrol, a quinone methide triterpenoid. Biochemical pharmacology, 72(10), 1311-1321. doi:10.1016/j.bcp.2006.08.014
12. Kim, J. E., Lee, M. H., Nam, D. H., Song, H. K., Kang, Y. S., Lee, J. E., ... & Han, K. H. (2013). Celastrol, an NF-κB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice. PloS one, 8(4), e62068.doi:10.1371/journal.pone.0062068
13. Abu Bakar, M. H., Cheng, K. K., Sarmidi, M. R., Yaakob, H., & Huri, H. Z. (2015). Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells. Molecules, 20(5), 8242-8269; doi:10.3390/molecules20058242