1258-84-0

Usage

Uses

Used in Anticancer Applications:
Pristimerin is used as an anticancer agent for its inhibitory effects on proteasome chymotrypsin subunit and cellular NF-κB pathway/IKK activation. It demonstrates anticancer efficacy both in vitro and in mice in vivo, including against imatinib/STI571-resistant cancer cells harboring the Bcr-Abl T315I mutation.
Used in Anti-inflammatory Applications:
Pristimerin is used as an anti-inflammatory agent due to its ability to inhibit tumor angiogenesis by targeting VEGFR2 activation and its known anti-inflammatory properties.
Used in Endocannabinoid System Regulation:
Pristimerin is used as a regulator of the endocannabinoid system for its potent inhibition of monoacylglycerol lipase (MAGL), which hydrolyzes the endocannabinoid 2-arachidonoyl glycerol (2-AG), thereby increasing its levels and extending its capacity to activate cannabinoid receptors.

Biological Activity

Potent and reversible inhibitor of monoacylglycerol lipase (MGL) (IC 50 = 93 nM). Also suppresses NF- κ B activation via inhibition of proteasome chymotrypsin-like activity and IKK α / β . Displays antitumor, anti-inflammatory and antimicrobial activities.

InChI:InChI=1/C30H40O4/c1-18-19-8-9-22-28(4,20(19)16-21(31)24(18)32)13-15-30(6)23-17-27(3,25(33)34-7)11-10-26(23,2)12-14-29(22,30)5/h8-9,16,23,32H,10-15,17H2,1-7H3

Upstream product

• 34157-83-0 celastrol 
• 74-88-4 methyl iodide 
• 75-09-2 dichloromethane 
• 34157-83-0 celastrol 
• 186581-53-3 diazomethane 

Downstream Products

• 121688-15-1 (2R,4aR,6bR,12bS,14aS)-6b,10,11-Trihydroxy-2,4a,6,9,12b,14a-hexamethyl-1,2,3,4,4a,5,6b,12b,13,14,14a,14b-dodecahydro-picene-2-carboxylic acid methyl ester 
• 114020-41-6 netzahualcoyene 
• 121688-16-2 C₆₀H₇₈O₉ 
• 121688-16-2 C₆₀H₇₈O₉ 

Relevant academic research and scientific papers

Synthesis of celastrol derivatives as potential non-nucleoside hepatitis B virus inhibitors

A series of para-quinone methide (pQM) moiety and C-20- modified derivatives of celastrol were synthesized and evaluated for their inhibitory effect on the secretion of HBsAg and HBeAg as well as the inhibitory effect against HBV DNA replication. The results suggested that amidation of C-20 carboxylic group could generate derivatives with good anti-HBV profile, among them compound 14 showed the best inhibitory activity on the secretion of HBsAg (IC50?=?11.9?μμ) and HBeAg (IC50?=?13.1?μμ) with SI of 3.3 and 3.0, respectively. In addition, 14 also showed potent inhibitory effect against HBV DNA replication (48.5?±?15.1%, 25?μM). This is, to our knowledge, the first report of celastrol derivatives as potential non-nucleoside HBV inhibitors.

Optimization and biological evaluation of celastrol derivatives as Hsp90–Cdc37 interaction disruptors with improved druglike properties

Heat shock protein 90 (Hsp90) as a molecular target for oncology therapeutics has attracted much attention in the last decade. The Hsp90 multichaperone complex has important roles in the growth and/or survival of cancer cells. Cdc37, as a cochaperone, associates kinase clients to Hsp90 and promotes the development of malignant tumors. Disrupting the Hsp90–Cdc37 interaction provides an alternative strategy to inhibit the function of Hsp90 for cancer therapy. Celastrol, as a natural product, can disrupt the Hsp90–Cdc37 interaction and induce degradation of kinase clients. The study conducted here attempted to elucidate the structure–activity relationship of celastrol derivatives as Hsp90–Cdc37 disruptors and to improve the druglike properties. 23 celastrol derivatives were designed, synthesized, and the biological activities and physicochemical properties were determined. The derivative CEL20 showed improved Hsp90–Cdc37 disruption activity, anti-proliferative activities as well as druglike properties. Additionally, CEL20 induced clients degradation, cell cycle arrest and apoptosis in Panc-1 cells. This study can provide reference for the discovery of novel Hsp90–Cdc37 disruptors.

SAR study of celastrol analogs targeting Nur77-mediated inflammatory pathway

Nur77, an orphan member of the nuclear receptor superfamily, plays an important role in the regulation of inflammatory processes. Our previous work found that celastrol, a pentacyclic triterpene, bound to Nur77 to inhibit inflammation in a Nur77-dependent

Synthesis of 3- and 29-substituted celastrol derivatives and structure-activity relationship studies of their cytotoxic activities

A series of 3-carbamate and 29-ester celastrol derivatives (compounds 1–26) were designed and synthesized. These analogues were evaluated for their cytotoxic activities against several cancer cell lines. Cytotoxicity data revealed that the properties of substituents and substitution position had important influence on cytotoxic activity. Modification of C-3 hydroxyl with size-limited groups did not reduce the activity obviously. The introduction of polarity group like piperazine could improve the solubility. Compound 23 was chosen to further evaluate anti-tumor efficacy in vivo. It showed higher inhibition rate and better safety than celastrol during in vivo experiment by intragastric administration. The preliminary antitumor studies of compound 23 in vivo showed that it might be promising for the development of new antitumor agents.

Scaffold hopping of celastrol provides derivatives containing pepper ring, pyrazine and oxazole substructures as potent autophagy inducers against breast cancer cell line MCF-7

Three series of celastrol derivatives, namely, 6a–6i, 11a–11i and 15a–15i, were designed based on the scaffold hopping strategy. The derivatives were synthesized and biologically evaluated against five human tumor cell lines (i.e. A549, MCF-7, Bel7402, HT-29 and PC3) using MTT assay in vitro. Results showed that compound 11i exhibited apparent antiproliferative activity against the MCF-7 cell line with an IC50 value of 1.31 μM and could remarkably inhibit the colony formation of the MCF-7 cells. Transmission electron microscopy assay, monodansylcadaverine incorporation assay and the expression of LC3 A/B, p62 and Beclin-1 in MCF-7 cells suggested that the potent antiproliferative activity of compound 11i was mainly due to its autophagy-inducing effect. Moreover, compound 11i could arrest the MCF-7 cells in the G2/M phase by regulating the cell-cycle-related proteins Cdk-1 and Cyclin B1. In the zebrafish xenograft model, compound 11i could obviously inhibit the proliferation of the MCF-7 cells. Thus, compound 11i could serve as a promising lead compound for breast cancer therapy.

Synthesis and biological evaluation of celastrol derivatives as potential anti-glioma agents by activating RIP1/RIP3/MLKL pathway to induce necroptosis

Celastrol, a quinone methide triterpenoid, possesses potential anti-glioma activity. However, its relatively low activity limit its application as an effective agent for glioma treatment. In search for effective anti-glioma agents, this work designed and

Synthesis and Biological Evaluation of Celastrol Derivatives with Improved Cytotoxic Selectivity and Antitumor Activities

Cdc37 associates kinase clients to Hsp90 and promotes the development of cancers. Celastrol, a natural friedelane triterpenoid, can disrupt the Hsp90-Cdc37 interaction to provide antitumor effects. In this study, 31 new celastrol derivatives, 2a - 2d , 3a - 3g , and 4a - 4t , were designed and synthesized, and their Hsp90-Cdc37 disruption activities and antiproliferative activities against cancer cells were evaluated. Among these compounds, 4f , with the highest tumor cell selectivity (15.4-fold), potent Hsp90-Cdc37 disruption activity (IC50= 1.9 μM), and antiproliferative activity against MDA-MB-231 cells (IC50= 0.2 μM), was selected as the lead compound. Further studies demonstrated 4f has strong antitumor activities both in vitro and in vivo through disrupting the Hsp90-Cdc37 interaction and inhibiting angiogenesis. In addition, 4f exhibited less toxicity than celastrol and showed a good pharmacokinetics profile in vivo. These findings suggest that 4f may be a promising candidate for development of new cancer therapies.

Celastrol-1,2,3-triazole derivative as well as preparation method and application thereof

The invention discloses a celastrol-1,2,3-triazole derivative as well as a preparation method and application thereof, and belongs to the technical field of medicines. The celastrol-1,2,3-triazole derivative disclosed by the invention is subjected to an in-vitro anti-proliferation activity test, test cells are A549, MCF7, HT29, H4, U251, A172, LN229 and U87, and an activity result shows that the synthesized compound has remarkable anti-tumor activity, and the anti-tumor activity of the partially synthesized compound is obviously superior to that of celastrol. The celastrol-1,2,3-triazole derivative disclosed by the invention has remarkable anti-glioma activity, has potential research value and application prospect, and is applied to treatment of tumor diseases, and the tumor diseases comprise lung cancer, breast cancer, colon cancer and glioma.

Tripterine derivative and preparation method and application thereof

The invention discloses a tripterine derivative and a preparation method and application thereof, and belongs to the technical field of medicines. The invention aims to provide a tripterine derivative with low toxicity and antitumor activity and a prepara

Synthesis and biological evaluation of celastrol derivatives as potential immunosuppressive agents

Celastrol, a friedelane-type triterpenoid isolated from the genus Triperygium, possesses antitumor, anti-inflammatory, and immunosuppressive activities. A total of 42 celastrol derivatives (1a?1t, 2a?2l, and 3a?3j) were synthesized and evaluated for their immunosuppressive activities. Compounds 2a?2e showed immunosuppressive effects, with IC50 values ranging from 25 to 83 nM, and weak cytotoxicity (CC50 > 1 μM). Compound 2a, with a selectivity index value 31 times higher than that of celastrol, was selected as a lead compound. Further research showed that 2a exerted its immunosuppressive effects by inducing apoptosis and inhibiting cytokine secretion via Lck- and ZAP-70-mediated signaling pathways.