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 (JSmol)	Interactive image;
ChemSpider	109405;
ECHA InfoCard	100.164.266
PubChem CID	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]^[11] Celastrol has also shown to possess (by inhibition of NF-κB in the hypothalamus^[12]) anti-diabetic effects on diabetic nephropathy and improve whole-body insulin resistance^[13]^[14]

References

↑ 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): 1873–6. doi:10.1016/j.bmcl.2010.01.152. PMID 20167482.
↑ 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.
↑ 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.
↑ 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.
↑ 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): 441–6. doi:10.3892/ijmm.2011.601. PMID 21249311.
↑ 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. PMC 3952546. PMID 19096011.
↑ 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.
↑ 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.
↑ 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.
↑ Pfuhlmann K, Schriever SC, Baumann P, Kabra DG, Harrison L, Mazibuko-Mbeje SE, Contreras RE, Kyriakou E, Simonds SE, Tiganis T, Cowley MA, Woods SC, Jastroch M, Clemmensen C, De Angelis M, Schramm KW, Sattler M, Messias AC, Tschöp MH, Pfluger PT (August 2018). "Celastrol Induced Weight Loss is Driven by Hypophagia and Independent From UCP1". Diabetes: db180146. doi:10.2337/db18-0146. PMID 30158241.
↑ 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. PMC 4768733. PMID 26000480.
↑ 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
↑ 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. PMC 3637455. PMID 23637966.
↑ 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. PMID 25961164.

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[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): 1873–6. doi:10.1016/j.bmcl.2010.01.152. PMID 20167482.

[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.

[Venkatesha-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): 441–6. 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. PMC 3952546. 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] Pfuhlmann K, Schriever SC, Baumann P, Kabra DG, Harrison L, Mazibuko-Mbeje SE, Contreras RE, Kyriakou E, Simonds SE, Tiganis T, Cowley MA, Woods SC, Jastroch M, Clemmensen C, De Angelis M, Schramm KW, Sattler M, Messias AC, Tschöp MH, Pfluger PT (August 2018). "Celastrol Induced Weight Loss is Driven by Hypophagia and Independent From UCP1". Diabetes: db180146. doi:10.2337/db18-0146. PMID 30158241.

[11] 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. PMC 4768733. PMID 26000480.

[12] 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

[13] 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. PMC 3637455. PMID 23637966.

[14] 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. PMID 25961164.