Bezafibrate

Manufactured by Merck Group

Sourced in United States, United Kingdom, Switzerland

Bezafibrate is a laboratory equipment product manufactured by Merck Group. It is a lipid-lowering agent that is used in the treatment of dyslipidemia. Bezafibrate functions by decreasing the levels of triglycerides and increasing the levels of high-density lipoprotein (HDL) cholesterol in the body.

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Close spelling variants of this product

Bezafibrate (BEZA),

36 protocols using bezafibrate

Structurally Diverse Glass Former Dataset

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A structurally diverse dataset (n = 26), composed of compounds previously classified as glass formers (GFs) when prepared by melt-quenching, solvent evaporation, or spray-drying methods, was included in the study [5 (link),7 (link),8 (link),9 (link),10 (link),18 (link)]. Only compounds supplied in their free crystalline form (i.e., no salts, solvates, hydrates, etc.), as confirmed by DSC analysis, were used.
Metolazone was purchased from API Chemical (Hangzhou, China). Acetaminophen, bezafibrate, clofoctol, chlorpropamide, dimethyl sulfoxide, glibenclamide, glipizide, hydrocortisone, sodium hydroxide, sodium phosphate, sodium chloride, sulfamerazine, sulfathiazole, and tinidazole were supplied by Sigma-Aldrich (Steinheim, Germany). Aripiprazole, cinnarizine, clotrimazole, droperidol, d-salicin, fenofibrate, flurbiprofen, hydrochlorothiazide, ibuprofen, ketoconazole, ketoprofen, prednisone, and probucol were obtained from Toronto Research Chemical (Toronto, ON, Canada). Indapamide and procaine were purchased from Tokyo Chemical Co. Ltd. (Tokyo, Japan). Acetone was supplied by Merck (Darmstadt, Germany), ethanol by Solveco (Rosersberg, Sweden), and phosphorus pentoxide by VWR (Leuven, Belgium). All of the chemicals used in this study were of either pharmaceutical or analytical grade with a specified purity of ≥ 97%.

Edueng K., Bergström C.A., Gråsjö J, & Mahlin D. (2019). Long-Term Physical (In)Stability of Spray-Dried Amorphous Drugs: Relationship with Glass-Forming Ability and Physicochemical Properties. Pharmaceutics, 11(9), 425.

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Pharmacological Regulators of Cell Signaling

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Rosiglitazone, Bezafibrate and Roscovitine were from Sigma Aldrich (Saint-Quentin Fallavier, France). GW 7647 was from Axon Medchem (Groningen, The Netherlands). GW 9662 and SR 11235 were from Santa Cruz Biotechnology (Santa Cruz, CA, USA).

Peiretti F., Montanari R., Capelli D., Bonardo B., Colson C., Amri E.Z., Grimaldi M., Balaguer P., Ito K., Roeder R.G., Pochetti G, & Brunel J.M. (2020). A novel N-substituted valine derivative with unique PPARγ binding properties and biological activities. Journal of medicinal chemistry, 63(21), 13124-13139.

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Intracerebroventricular Streptozotocin Injection and Bezafibrate Treatment

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Previously described procedures of ICV administration of STZ were implemented with minor modifications [37 (link),54 (link)]. Briefly, rats were deeply anesthetized and restrained in a stereotaxic apparatus (Stoelting, Wood Dale, IL, USA). STZ (Sigma–Aldrich, Saint Louis, MO, USA) was freshly dissolved in aCSF, and a solution of 25 mg/mL was prepared. ICV injection was performed bilaterally with STZ (3 mg/kg) in two divided doses, on days 1 and 3 (i.e., 0.75 mg/kg into each lateral ventricle per day) or with the same volume of aCSF. The coordinates were 0.8 mm posterior to the bregma, 1.5 mm bilateral to the sagittal suture, and 3.6 mm below the dura. Bezafibrate powder (Sigma–Aldrich) was dissolved in sterile corn oil at 40 °C to obtain a suspension with a final concentration of 50 mg/mL. Bezafibrate or vehicle (corn oil) was intraperitoneally injected once a day from days 1 to 28. The dose of Bezafibrate IP injection was 50 mg/kg/day, which has been used to reduce the inflammatory response in rats [55 (link)].

Lin L.F., Jhao Y.T., Chiu C.H., Sun L.H., Chou T.K., Shiue C.Y., Cheng C.Y, & Ma K.H. (2022). Bezafibrate Exerts Neuroprotective Effects in a Rat Model of Sporadic Alzheimer’s Disease. Pharmaceuticals, 15(2), 109.

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Agonist-Induced Cell Culture Study

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Human MKPL-1, MOLM-13, K562, and Jurkat cells were cultured in RPMI1640 medium containing 10% FBS, 1% penicillin/streptomycin. 293T cells were cultured in DMEM medium containing 10% FBS, 1% penicillin/streptomycin. For agonists treatment, cells were cultured with 9-cis-RA (1μM, Sigma-Aldrich #R4643), ATRA (1μM, Sigma-Aldrich #R2625), Bezafibrate (60μM, Sigma-Aldrich #B9273), Fenofibrate (30μM, Sigma-Aldrich #F6020), GW0742 (0.05μM, Sigma-Aldrich #G3295) or Rosiglitazone (5μM, Sigma-Aldrich #R2408) for 48–72h, respectively. All cultures were incubated at 37°C in 5% CO₂. All cell lines were tested for mycoplasma contamination. No cell lines used in this study were found in the database of commonly misidentified cell lines that are maintained by ICLAC and NCBI BioSample.

Li K., Zhang Y., Liu X., Liu Y., Gu Z., Cao H., Dickerson K.E., Chen M., Chen W., Shao Z., Ni M, & Xu J. (2020). Non-Coding Variants Connect Enhancer Dysregulation with Nuclear Receptor Signaling in Hematopoietic Malignancies. Cancer discovery, 10(5), 724-745.

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Pharmaceutical Compounds and Oligonucleotide Synthesis

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1,4-Bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), bezafibrate, and fenofibrate were purchased from Sigma-Aldrich (St. Louis, MO, USA). Sodium phenobarbital was purchased from FUJIFILM Wako Pure Chemicals (Osaka, Japan). Oligonucleotides were synthesized by Macrogen (Seoul, Korea). All other reagents were obtained from FUJIFILM Wako Pure Chemical or Sigma-Aldrich unless otherwise indicated.

Shizu R., Otsuka Y., Ishii C., Ezaki K, & Yoshinari K. (2023). PPARα Induces the Expression of CAR That Works as a Negative Regulator of PPARα Functions in Mouse Livers. International Journal of Molecular Sciences, 24(4), 3953.

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Metabolic Analysis of K562 Cells

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K562 cells were cultured and polar cell extracts were prepared as described before [4 (link)]. For tracer-based metabolic analysis, standard glucose- or glutamine-free RPMI-1640 media (Gibco) was used and substituted with 2 g/l [1,2-¹³C]glucose or 300 mg/l [3-¹³C]glutamine (Isotec, Sigma), respectively. 5 × 10⁷ exponentially growing K562 cells per control or treatment were pelleted by centrifugation at 8000g for 5 min and resuspended in the relevant media with BaP or solvent controls and incubated for 24 or 3 h at 37 °C and 5 % CO₂ in a humidified incubator. For BaP treatment, bezafibrate 0.5 mM and medroxyprogesterone acetate 5 μM (Sigma) or the equivalent concentrations of DMSO and ethanol solvent control were added to the media at T = 0 h.
For 3-h labelling of 24-h drug treatments, media was exchanged for the last 3 h with media supplemented with labelled glucose or glutamine plus BaP or solvent control. All samples were dissolved in 100 mM phosphate buffer with 10 % D₂O and 500 μM Trimethylsilylpropanoic acid (TMSP) added.

Reed M.A., Ludwig C., Bunce C.M., Khanim F.L, & Günther U.L. (2016). Malonate as a ROS product is associated with pyruvate carboxylase activity in acute myeloid leukaemia cells. Cancer & Metabolism, 4, 15.

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Cell Culturing and Compound Treatments

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Cells were grown in Dulbecco’s Modified Eagle Medium (DMEM), Corning Life Sciences, Manassas, VA, containing high glucose levels (4.5 g/L) or in DMEM devoid of glucose for 48–72 hr. Both media were supplemented with 10% fetal bovine serum, 4 mM glutamine, 100 IU penicillin and 100 μg/mL streptomycin, Corning Life Sciences, Manassas, VA. In some experiments, ACAD9 deficient fibroblasts were incubated for 24 hr with JP4-039 (40 or 200 nM), obtained from Dr. Peter Wipf, Department of Chemistry, University of Pittsburgh^{50 (link)}, N-acetylcysteine (1 mM), Sigma-Aldrich Co., St. Louis, MO, resveratrol (5 µM), Sigma-Aldrich Co., St. Louis, MO, mitoQ (200 nM), MitoQ Limited, Auckland, New Zealand, Trolox (a hydrosoluble analogue of vitamin E; 1 mM), Sigma-Aldrich Co., St. Louis, MO, or bezafibrate (600 µM), Sigma-Aldrich Co., St. Louis, MO, prior to the analysis of parameters.

Leipnitz G., Mohsen A.W., Karunanidhi A., Seminotti B., Roginskaya V.Y., Markantone D.M., Grings M., Mihalik S.J., Wipf P., Van Houten B, & Vockley J. (2018). Evaluation of mitochondrial bioenergetics, dynamics, endoplasmic reticulum-mitochondria crosstalk, and reactive oxygen species in fibroblasts from patients with complex I deficiency. Scientific Reports, 8, 1165.

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Polymer Hydrogel Synthesis and Characterization

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A PSaMA sodium salt solution
13% (M_w 350,000), PScMA partial isobutyl
ester (M_w 65,000 g·mol^–1), polyethylene glycol (PEG) (M_w 200
g·mol^–1, PEG 200; M_w 400 g·mol^–1, PEG 400; M_w 600 g·mol^–1, PEG 600; M_w 1500 g·mol^–1, PEG 1500; M_w 2000 g·mol^–1, PEG 2000),
and polyethyleneimine (PEI), branched (M_n 600 g·mol^–1, PEI 600) were purchased from
Sigma-Aldrich. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS), atenolol, atrazine, bezafibrate,
bisphenol A, bromothymol blue, naproxen, phenolphthalein, sulphamethoxazole,
oil red EGN, n-hexadecane, magnesium sulfate, magnesium
chloride, sodium sulfate, sodium dodecyl sulfate (SDS), sodium hydroxide,
glacial acetic acid, sodium phosphate monobasic dihydrate, phosphoric
acid 85%, and hydrochloric acid 37% were bought from Sigma-Aldrich.
Ethanol of 100% technical grade was bought from Boom B.V. n-Hexane 99+% was purchased from Acros Organics. Sodium
chloride (Sanal P) was received from AkzoNobel. Deionized water (DI,
1.0 μS·cm^–1) was used for the preparation
of coagulation baths and Milli-Q water (Millipore, 0.6 μS·cm^–1) was used to prepare solutions. The PSaMA solution
was dried for 16 h at 100 °C to obtain the solid polymer which
was used without further purification. All other chemicals were used
as received.

Nielen W.M., Willott J.D, & de Vos W.M. (2020). Aqueous Phase Separation of Responsive Copolymers for Sustainable and Mechanically Stable Membranes. ACS Applied Polymer Materials, 2(4), 1702-1710.

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Evaluation of Molecular Compounds

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Bezafibrate, rifampicin, rifaximin, simvastatin, and SR12813 were purchased from Sigma-Aldrich (St. Louis, MO, USA). Oligonucleotides were commercially synthesized by Macrogen (Seoul, Korea). All other reagents were obtained from FUJIFILM Wako Pure Chemical (Osaka, Japan) or Sigma-Aldrich, unless otherwise indicated.

Shizu R., Ezaki K., Sato T., Sugawara A., Hosaka T., Sasaki T, & Yoshinari K. (2021). PXR Suppresses PPARα-Dependent HMGCS2 Gene Transcription by Inhibiting the Interaction between PPARα and PGC1α. Cells, 10(12), 3550.

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NMR Spectroscopy of Lipid-Lowering Drugs

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The spectra were recorded at 300 K on a Bruker Avance III 400 MHz NMR with a broadband probe and analyzed using the Bruker Topspin software package [24 ]. Bezafibrate (Sigma lot: 046k1113), gemfibrozil (Sigma lot: 65H0084), and clofibric acid (Aldrich lot: 01220BT) were purchased commercially and used without further modification. Fen was synthesized from fenofibrate as previously reported and characterized [12 (link)]. Each compound was dissolved in acetone-d₆ (99.9 atom % D) with 0.3% TMS, purchased from Sigma. ¹H spectra utilized the zg30 pulse program [24 ], with digital quad detection (DQD) acquisition mode. For each spectrum, 128 scans were collected with a D1 delay of 2.0 s; a 90° pulse time of 7.83 μs; a sweep width (sw) range of 20.55-20.68 ppm; o1 signal range of 2470.79-2471.09 Hz; and the receiver gain set to 143.7 for Beza, 645.1 for Clo, 12.7 for Gem, and 181 for Fen. ¹³C spectra were run proton decoupled (pulse program zgpg30) with qsim acquisition mode, 1024 scans, a 90° pulse time of 14.90 μs, and a D1 delay of 2.0 s. The sw range was 238.32-238.88 ppm, the ¹³C o1 range was 10060.80-10061.31 Hz, the ¹H o2 range was 1600.52-1600.60 Hz, and the receiver gain was 181 for Beza, 203.2 for Clo, and 2050 for Fen and Gem.

Miller C., Schildcrout S., Mettee H, & Balendiran G. (2022). Molecular dynamics of fibric acids. European journal of chemistry (Print), 13(2), 186-195.

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