1258-84-0

Basic information

• Product Name: pristimerin
• Synonyms: pristimerin;3-Hydroxy-2-oxo-24-nor-D:A-friedoolean-1(10),3,5,7-tetren-29-oic acid methyl ester;Celastrol-methylether;(9b,13a,14b,20a)-3-Hydroxy-9,13-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tertraen-29-oic acid methyl ester;(9β,13α,14β,20α)-3-Hydroxy-9,13-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oicacidmethylester;3-hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid, methyl ester;Celastrol methyl ester;Pristimerin(NSC 99281)
• CAS NO: 1258-84-0
• Molecular Formula: C₃₀H₄₀O₄
• Molecular Weight: 464.642
• Mol File: 1258-84-0.mol
• Article Data: 14

Chemical Properties

• Melting Point: 219.5°C
• Boiling Point: 488.1°C (rough estimate)
• Flash Point: 195.1°C
• Appearance: orange/
• Density: 1.0271 (rough estimate)
• Vapor Pressure: 2.63E-17mmHg at 25°C
• Refractive Index: 1.4800 (estimate)
• Storage Temp.: Store at -20°C
• Solubility: DMSO: ≥5mg/mL
• PKA: 8.60±0.70(Predicted)
• CAS DataBase Reference: pristimerin(CAS DataBase Reference)
• NIST Chemistry Reference: pristimerin(1258-84-0)
• EPA Substance Registry System: pristimerin(1258-84-0)

Safety Data

• Hazardous Substances Data: 1258-84-0(Hazardous Substances Data)

Usage

Description

Monoacylglycerol lipase (MAGL) hydrolyzes the endogenous cannabinoid 2-arachidonoyl glycerol (2-AG), terminating its capacity to activate cannabinoid receptors. Pristimerin is a naturally occurring terpenoid that potently inhibits MAGL (IC50 = 93 nM). Its actions are rapid, reversible, and noncompetitive. Pristimerin (1 μM) significantly increases 2-AG levels in isolated rat neurons, indicating that it inhibits endogenous MAGL in cultured cells. Moreover, it does not increase levels of palmitoyl ethanolamide, suggesting that pristimerin does not affect the activity of fatty acid amide hydrolase (FAAH).

Uses

Pristimerin is a triterpenoid that inhibits tumor angiogenesis by targeting VEGFR2 activation and is known to exhibit anti-inflammatory properties.

General Description

A cell-permeable plant dienone-phenolic triterpenoid, naturally isolated from tripterygium wilfordii, whose inhibitory activities against proteasome chymotrypsin subunit (IC50 = 2.2 and 3.0 μM against purified rabbit 20S and human 26S proteasome, respectively) and cellular NF-κB pathway/IKK activation most likely account for its reported anticancer efficacy both in vitro (IC50 ≤610 nM in A549, K562, KBM5, MCF-7, MDA-MB-231, HepG2, and primary human leukemia cell cultures) and in mice in vivo (1 to 2.5 mg/kg/day, s.c.), including imatinib/STI571-resistant cancer cells harboring Bcr-Abl T315I mutation. Also reported to inhibit the activity of monoacylglycerol lipase (MGL), the enzyme that hydrolyzes and deactivates the cannabionoid receptor ligand 2-Arachidonoyl-sn-glycerol (2-AG), in a reversible manner with high potency (IC50 = 93 nM).

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

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

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 articles and documents

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.

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

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 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.

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