Rosiglitazone-maleate-BRL-49653C-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERosiglitazone maleateCat. No.: HY-14600CAS No.: 155141-29-0Synonyms: BRL 49653C分式: CHNOS分量: 473.5作靶點(diǎn): PPAR; TRP Channel; Autophagy; Autophagy作通路: Cell Cycle/DNA Damage; Membrane Transporter/Ion Channel;Neuronal Signaling; Autoph

2、agy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) H2O : 2 mg/mL (4.22 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.1119 mL 10.5597 mL 21.1193 mL5 mM - - -10 mM - - -請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Rosigli

3、tazone maleate種有效的，選擇性的 PPAR 激活劑，對(duì) PPAR1，PPAR2 和 PPAR 的 EC50值分別為 30 nM，100 nM 和 60 nM，對(duì) PPAR 的 Kd 值約為 40 nM；Rosiglitazone maleate 同時(shí)為 TRPchannels 的調(diào)節(jié)劑，可抑制 TRPM2, TRPM3 的活性，激活 TRPC5。IC50 & Target PPAR1 PPAR21/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE30 nM (EC50) 100 nM (EC50)體外研究 Rosiglitazone

4、maleate is a potent and selective activator of PPAR, with EC50s of 30 nM and 100 nM forPPAR1 and PPAR2, respectively, and a Kd of appr 40 nM for PPAR. Rosiglitazone (BRL49653, 0.1, 1,10M) promotes differentiation of C3H10T1/2 stem cells to adipocytes 1. Rosiglitazone (Compound 6)activates PPAR, with

5、 an EC50 of 60 nM 2. Rosiglitazone (1 M) activates PPAR, which binds to NF-1promoter to activate gene transcription in neurons. Rosiglitazone (1 M) also protects Neuro2A cells andhippocampal neurons against oxidative stress, and up-regulates BCL-2 expression in an NF-1-dependentmanner 3. Rosiglitazo

6、ne completely inhibits TRPM3 with IC50 values of 9.5 and 4.6 M against nifedipine-and PregS-evoked activity, but such effects are not via PPAR. Rosiglitazone inhibits TRPM2 at higherconcentration, with an IC50 of appr 22.5 M. Rosiglitazone is a strong stimulator of TRPC5 channels, with anEC50 of -30

7、 M 4.體內(nèi)研究 Rosiglitazone (5 mg/kg, p.o.) decreases the serum glucose in diabetic rats. Rosiglitazone also decreases IL-6, TNF-, and VCAM-1 levels in diabetic group. Rosiglitazone in combination with losartan increases glucosecompared to diabetic and Los-treated groups. Rosiglitazone significantly ame

8、liorates endothelial dysfunctionindicated by a significantly lower contractile response to PE and Ang II and enhancement of ACh-provokedrelaxation in aortas isolated from diabetic rats 5.PROTOCOLKinase Assay 1 cDNA encoding amino acids 174-475 of PPAR1 is amplified via polymerase chain reaction and

9、inserted intobacterial expression vector pGEX-2T. GST-PPAR LBD is expressed in BL21(DE3)plysS cells and extracts.For saturation binding analysis, bacterial extracts (100 g of protein) are incubated at 4C for 3 h in buffercontaining 10 mM Tris (pH 8.0), 50 mM KCl, 10 mM dithiothreitol with 3H-BRL4965

10、3 (specific activity, 40Ci/mmol) in the presence or absence of unlabeled Rosiglitazone. Bound is separated from free radioactivityby elution through 1-mL Sephadex G-25 desalting columns. Bound radioactivity eluted in the column voidvolume and is quantitated by liquid scintillation counting 1.MCE has

11、 not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 C3H10T1/2 cells are grown in a 24-well plate in DME medium supplemented with 10% fetal calf serum.Medium and compound (Rosiglitazone) are exchanged every 3 days. Cells are stained at day 7 with Oil R

12、edO and photographed 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats are intravenously injected with 38 mg/kg streptozotocin and after 48 h, diabetes is identified by urinaryAdministration 2 glucosuria and then random blood sugar is measur

13、ed and this day is regarded as day 0. Animals with aserum glucose level of 220-300 mg/dL are selected to be used in this study. Rats are randomly separatedinto five groups for daily drug administration for 8 weeks: group 1: control nondiabetic rats given a vehicleonly (0.5 mL/kg of 0.5% carboxy meth

14、yl celleluse orally), group 2: control diabetic rats given a vehicle, group3: diabetic rats receiving Rosiglitazone (5 mg/kg orally), group 4: diabetic rats receiving losartan (2 mg/kg,orally), and group 5: diabetic rats receiving both Rosiglitazone and losartan 2.MCE has not independently confirmed

15、 the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Free Radic Biol Med. 2018 Aug 21;126:259-268. J Cell Physiol. 2019 Apr 15. PPAR Res. 2019 Jul 1;2019:2715176. PPAR Res. 2019 Jul. Front Mol Neurosci. 2017 Sep 14;10:293.See more c

16、ustomer validations on HYPERLINK / www.MedChemEREFERENCES1. Lehmann JM, et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPARgamma). J Biol Chem. 1995 Jun 2;270(22):12953-6.2. Willson TM, et al. The structure-activity relationsh

17、ip between peroxisome proliferator-activated receptor gamma agonism and theantihyperglycemic activity of thiazolidinediones. J Med Chem. 1996 Feb 2;39(3):665-8.3. Thouennon E, et al. Rosiglitazone-activated PPAR induces neurotrophic factor-1 transcription contributing to neuroprotection. JNeurochem. 2015 Aug;134(3):463-70.4. Majeed Y, et al. Rapid and contrasting effects of rosiglitazone on transient receptor potential TRPM3 and TRPC5 channels. MolPharmacol. 2011 Jun;79(6):1023-30.5. Ateyya H, et al. Beneficial effects of rosiglitazone and losartan combina