Celastrol

製品コードS1290 バッチS129003

印刷

化学情報

Chemical Structure Synonyms NSC 70931, Tripterine Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C29H38O4
分子量 450.61 CAS No. 34157-83-0
Solubility (25°C)* 体外 DMSO 90 mg/mL (199.72 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

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生物活性

製品説明 Celastrol is a potent proteasome inhibitor for the chymotrypsin-like activity of a purified 20S proteasome with IC50 of 2.5 μM. Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway. Celastrol inhibits dopaminergic neuronal death of Parkinson's disease through activating mitophagy.
in vitro Celastrol at 5 μM inhibits the chymotrypsin-like, PGPH-like, and trypsin-like activities of the purified 20S proteasome by 80%, 5%, and <1%, respectively, whereas at 10 μM, it inhibits these three proteasomal activities by ∼90%, 15%, and <1%, respectively. Celastrol significantly inhibits the proteasomal chymotrypsin activity in PC-3 cells in a concentration-dependent manner. Celastrol at 2.5 μM to 5 μM induces caspase-3 activity by 4.7-fold to 5.5-fold in PC-3 cells. Celastrol (5 μM) treated cells, the levels of the proteasome target proteins, IκB-α and Bax, are increased after 1 hour and further increased to its peak for 4 hours to 12 hours. Celastrol (2.5 μM) treatment induces proteasome inhibition by 40%, as shown by the decreased levels of chymotrypsin-like activity and increased accumulation of ubiquitinated proteins in LNCaP cells. Celastrol (2.5 μM) induces apoptosis in the Celastrol-treated LNCaP cells, as shown by increased levels of caspase-3 activity (up to 3.5-fold), PARP cleavage, and apoptotic morphology. [1] Celastrol (300 nM) is found to suppress LPS-induced production of TNF-alpha and IL-1beta by human monocytes and macrophages. Celastrol (100 nM) also decreases LPS-induced expression of class II MHC molecules by microglia. Celastrol strongly inhibits LPS and IFN-y-induced NO production with IC50 of 200 nM in macrophage lineage cells. Celastrol strongly inhibits TNF-α and IFN-γ-induced NO production with IC50 of 200 nM in endothelial cells. [2] Celastrol (2.5 μM) potentiates the apoptosis induced by TNF and chemotherapeutic agents and inhibits invasion, both regulated by NF-kappaB activation, in KBM-5 cells. Celastrol (2.5 μM) suppresses the expression of TNF induced the expression of gene products involved in antiapoptosis (IAP1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin), proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) in KBM-5 cells. Celastrol (5 μM) is found to inhibit the TNF-induced activation of IkappaBalpha kinase, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 nuclear translocation and phosphorylation, and NF-kappaB-mediated reporter gene expression. [3] Celastrol inhibits proliferating of RPMI 8226, KATOIII, UM-SCC1, U251MG and MDA-MB-231 cells with IC50 of 0.52 μM, 0.54 μM, 0.76 μM, 0.69 μM and 0.67 μM, respectively. Celastrol (1 μM) inhibits growth of RPMI 8226 with a decrease in the levels of cyclin D1 and cyclin E, but concomitant increase in the levels of p21 and p27. Celastrol induces apoptosis in RPMI-8226 cells indicated by the activation of caspase-8, bid cleavage, caspase-9 activation, caspase-3 activation, PARP cleavage and through the down regulation of anti-apoptototic proteins. Celastrol (1 μM) suppresses Akt pathway and activates JNK kinase in RPMI-8226 cells. [4]
in vivo Celastrol (3 mg/kg) results in significant inhibition (up to 70%) of tumor growth in male nude mice bearing PC-3 tumors, associated with increased p27 levels and Bax level. Celastrol (3 mg/kg) results more apoptotic tumor cells with the appearance of various PARP cleavage fragments in tumor of male nude mice bearing PC-3 tumors. Celastrol (3 mg/kg) causes 35% of tumor inhibition, associated with decreased proteasome activity and decreased expression of AR protein in nude mice bearing C4-2B tumors. [1] Celastrol (3 mg/kg) is found to suppress strongly joint swelling and other manifestations of adjuvant arthritis in mice. Celastrol (0.2 mg/kg) significantly improves the performance in memory, learning and psychomotor activity tests in rats. [2]
特徴 A potent antioxidant and anti-inflammatory drug.

プロトコル(参考用のみ)

キナーゼアッセイ Inhibition of purified 20S proteasome activity
A purified rabbit 20S proteasome (0.1 μg) is incubated with 40 μM of various fluorogenic peptide substrates in 100 μL assay buffer (20 mM Tris-HCl (pH 7.5)), in the presence of Celastrol at different concentrations or in the solvent DMSO for 2 hours at 37 ℃, followed by measurement of inhibition of each proteasomal activity.
細胞アッセイ 細胞株 RPMI 8226, KATOIII, UM-SCC1, U251MG and MDA-MB-231 cells
濃度 ~5 μM
反応時間 2 hours
実験の流れ The anti-proliferative effect of celastrol on various human tumor cell lines is determined by the MTT uptake method. Briefly, 5×103 cells are incubated with Celastrol in triplicate in a 96-well plate at 37 ℃. MTT solution is then added to each well. After a 2 hours incubation at 37 ℃, extraction buffer (20% SDS, 50% dimethylformamide) is added, cells are incubated overnight at 37 ℃, and the optical density is then measured at 570 nm using a Tecan plate reader.
動物実験 動物モデル nude mice bearing C4-2B tumors
投薬量 3 mg/kg
投与方法 Intraperitoneal injection

カスタマーフィードバック

, , Oncotarget, 2016, 7(20):29648-63.

Data from [Data independently produced by , , Eur J Med Chem, 2017, 136:63-73]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

A NRF2-induced secretory phenotype activates immune surveillance to remove irreparably damaged cells [ Redox Biol, 2023, 66:102845] PubMed: 37597423
A NRF2-induced secretory phenotype activates immune surveillance to remove irreparably damaged cells [ Redox Biol, 2023, 66:102845] PubMed: 37597423
Celastrol targeting Nedd4 reduces Nrf2-mediated oxidative stress in astrocytes after ischemic stroke [ J Pharm Anal, 2023, 13(2):156-169] PubMed: 36908855
Celastrol alleviates oxidative stress induced by multi-walled carbon nanotubes through the Keap1/Nrf2/HO-1 signaling pathway [ Ecotoxicol Environ Saf, 2023, 252:114623] PubMed: 36774793
Celastrol inhibits necroptosis by attenuating the RIPK1/RIPK3/MLKL pathway and confers protection against acute pancreatitis in mice [ Int Immunopharmacol, 2023, 117:109974] PubMed: 37012867
Network Pharmacology and Experimental Validation to Explore That Celastrol Targeting PTEN is the Potential Mechanism of Tripterygium wilfordii (Lév.) Hutch Against IgA Nephropathy [ Drug Des Devel Ther, 2023, 17:887-900] PubMed: 36992900
Celastrol attenuates streptozotocin-induced diabetic cardiomyopathy in mice by inhibiting the ACE / Ang II / AGTR1 signaling pathway [ Diabetol Metab Syndr, 2023, 15(1):186] PubMed: 37700366
Network Pharmacology and Experimental Validation to Explore That Celastrol Targeting PTEN is the Potential Mechanism of Tripterygium wilfordii (Lév.) Hutch Against IgA Nephropathy [ Drug Des Devel Ther, 2023, 17:887-900] PubMed: 36992900
Lipopolysaccharide Activating NF-kB Signaling by Regulates HTRA1 Expression in Human Retinal Pigment Epithelial Cells [ Molecules, 2023, 28(5)2236] PubMed: 36903482
Quantitative chemical proteomics reveals anti-cancer targets of Celastrol in HCT116 human colon cancer cells [ Phytomedicine, 2022, 101:154096] PubMed: 35452923

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人間や獣医の診断であるか治療的な使用のためにでない。

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