Bezafibrate

製品コードS4159 バッチS415902

印刷

化学情報

Chemical Structure Synonyms BM 15075 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H20ClNO4
分子量 361.82 CAS No. 41859-67-0
Solubility (25°C)* 体外 DMSO 72 mg/mL (198.99 mM)
Ethanol 60 mg/mL (165.82 mM)
Water 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Bezafibrate (BM 15075) is the first clinically tested dual and pan-PPAR co-agonism.
in vitro Bezafibrate is a lipid-lowering fibric acid derivative. Bezafibrate binds to xPPARβ with EC50 of 5 μM. Bezafibrate transcriptionally activates the PPARβ of Xenopus with EC50 of 1 μM. [1] Bezafibrate exposure to rat primary culture of adipocytes for 24 h increases the mRNA levels of crucial genes involved in peroxisomal and mitochondrial β-oxidation. The mRNA levels of the peroxisomal β-oxidation rate-limiting enzyme acyl-CoA oxidase and of the muscle-type carnitine palmitoyl transferase I (M-CPT-I) increases by 1.6-fold and 4.5-fold, respectively. Bezafibrate induces an increase in the transcript levels of the uncoupling protein-2 (UCP-2; 1.5-fold induction) and UCP-3 (3.7-fold induction), mitochondrial proteins that reduce ATP yield and may facilitate the oxidation of fatty acids. Furthermore, Bezafibrate increases the mRNA levels of the fatty acid translocase (2-fold induction). Bezafibrate causes a 1.9-fold induction in 9,10-[3H]palmitate oxidation. Moreover, Bezafibrate reduces the mRNA expression of several adipocyte markers, including PPARγ (30% reduction), tumor necrosis factor-α (33% reduction), and the ob gene (26% reduction). The reduction of the adipocyte markers causes by Bezafibrate is accompanied by an increase in the mRNA levels of the preadipocyte marker Pref-1 (1.6-fold induction). [2]
in vivo Bezafibrate treatment is able to induce increasing mRNA levels of M-CPT-I (4.5-fold induction), fatty acid translocase (2.6-fold induction) and Pref-1 (5.6-fold induction) in epididymal white adipose tissue of rats. Similarly, increases. [2] Bezafibrate feeding causes a significant increase in liver weight in wild-type and PPARβ-null mice compared to controls, while liver weight is unchanged in Bezafibrate-fed PPAR-α null mice. Gonadal adipose stores are significantly smaller in wild-type and PPARβ-null mice fed Bezafibrate than in controls (2.8-fold less and ~2.6-fold less, respectively), and this effect is not found in similarly fed PPARα-null mice. Bezafibrate is able to cause changes of mRNAs encoding lipid metabolizing enzymes (such as AOX , cytochrome P450 4A (CYP4A), LPL, ACS, and LCA D) in wild-type, PPARβ-null mice and PPARα-null mice compared to controls. [3] Bezafibrate is able to induce UCPs expression, and modify energy homeostasis by directly inducing aco gene expression (14.5-fold at 7 days) and peroxisomal fatty acid β-oxidation in white adipose tissue of rats. Further, Bezafibrate significantly reduces plasma triglyceride and leptin concentrations, without modifying the levels of PPARγ or ob gene in white adipose tissue. [4]

プロトコル(参考用のみ)

キナーゼアッセイ CARLA pulldown assay
One milliliter of overnight cultures of Escherichia coli BL2 strain, transformed with the GST-PPAR LBD fusion plasmids, is used to inoculate 50 mL of LB medium. The bacteria are incubated at 37 ℃ until the culture reached A600 of 0.6. At that point, IPTG is added at final concentration of 0.1 mM, and the culture is incubated for a further 3h at 28 ℃. Bacterial cells are harvested by centrifugation and suspended in one tenth of the culture volume in NETN buffer (20 mM Tris-HCl, pH 8.0, 100 mM NaCl, 1 mM EDTA, 0.5% Nonidet P40) supplemented with 1 mM dithiothreitol, 0.5% dry milk, and protease inhibitors. Bacteria cells are then lysed by mild sonication. After centrifugation to remove the cell debris, glutathione Sepharose 4B beads equilibrated in NETN are added to the sonication extracts (250 mL of beads suspension per 50 mL of culture volume), and the GST-PPAR LBD fusions are allowed to bind to the beads for 1h at 4 ℃ with constant rotation. The glutathione-bound fusion proteins are washed several times with NETN and are resuspended in the appropriate volume of the same buffer. CARLA is performed in a total volume of 1 mL per reaction containing 2–3 mg of fusion protein. In each reaction, 20 mL of a 1:10 dilution in NETN of 35S-labeled, in vitro translated SRC-1 are added in ice (0.2% final concen-tration of translation reaction mix). The compounds tested are added at the appropriate concentrations. Probucol and nervonic acid initially precipitated in ice but are completely dissolved at 4 ℃. After incubation of the reaction mixture for 4 h at 4℃ with constant rotation, the immobilized fusion proteins are washed three times with 0.5 mL NETN, without milk. The glutathione-Sepharose-bound proteins are dried under vacuum before being resuspended in SDS sample buffer and subjected to SDS-PAGE. Before being dried and exposed to autoradiography, the polyacrylamide gels are lightly stained with Coomasie brilliant blue to control that equal quantities of fusion proteins are used in each reaction. The amounts of retained SRC-1 are determined by image analysis on a GS 250 molecular Imager instrument.

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：

Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome [ Nat Commun, 2021, 12(1):1929] PubMed: 33771987
Targeting the EZH2-PPAR Axis Is a Potential Therapeutic Pathway for Pancreatic Cancer [ PPAR Res, 2021, 2021:5589342] PubMed: 34335707

長期の保管のために-20°Cの下で製品を保ってください。

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。