罗格列酮作用机制 - Medchemexpress - MCE中国

1、Product Data SheetRosiglitazoneCat. No.: HY-17386CAS No.: 122320-73-4分式: CHNOS分量: 357.43作靶点: PPAR; TRP Channel; Autophagy; Ferroptosis作通路: Cell Cycle/DNA Damage; Membrane Transporter/Ion Channel; NeuronalSignaling; Autophagy; Apoptosis储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1

2、month溶解性数据体外实验 DMSO : 110 mg/mL (307.75 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 2.7978 mL 13.9888 mL 27.9775 mL5 mM 0.5596 mL 2.7978 mL 5.5955 mL10 mM 0.2798 mL 1.3989 mL 2.7978 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80

3、C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolub

4、ility: 2.75 mg/mL (7.69 mM); Clear solution此案可获得 2.75 mg/mL (7.69 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 27.5 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.75 mg/mL (7.69 mM); Clear solutionPage 1 o

5、f 2 www.MedChemE此案可获得 2.75 mg/mL (7.69 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 27.5 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.75 mg/mL (7.69 mM); Clear solution此案可获得 2.75 mg/mL (7.69 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 27.5 mg/m

6、L 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Rosiglitazone (BRL 49653) ，100 nM 和 60 nM1。种选择性的PPAR 激活剂，对 PPAR1，PPAR2 和 PPAR 的EC50 分别为 30 nMIC & Target PPAR1 PPAR2 TRPC5 TRPM230 nM (EC50) 100 nM (EC50)TRPM3体外研究 Rosiglitazone is a potent and selective activator of PPAR, with EC50s of 30 nM and

7、100 nM for PPAR1 and PPAR2,respectively, and a Kd of appr 40 nM for PPAR. Rosiglitazone (BRL49653, 0.1, 1,10 M) promotes differentiation ofC3H10T1/2 stem cells to adipocytes1. Rosiglitazone (Compound 6) activates PPAR, with an EC50 of 60 nM2.Rosiglitazone (1 M) activates PPAR, which binds to NF-1 pr

8、omoter to activate gene transcription in neurons.Rosiglitazone (1 M) also protects Neuro2A cells and hippocampal neurons against oxidative stress, and up-regulatesBCL-2 expression in an NF-1-dependent manner3. Rosiglitazone completely inhibits TRPM3 with IC50 values of 9.5and 4.6 M against nifedipin

9、e- and PregS-evoked activity, but such effects are not via PPAR. Rosiglitazone inhibitsTRPM2 at higher concentration, with an IC50 of appr 22.5 M. Rosiglitazone is a strong stimulator of TRPC5 channels,with an EC50 of -30 M4.体内研究 Rosiglitazone (5 mg/kg, p.o.) decreases the serum glucose in diabetic

10、rats. Rosiglitazone also decreases IL-6, TNF-,and VCAM-1 levels in diabetic group. Rosiglitazone in combination with losartan increases glucose compared todiabetic and Los-treated groups. Rosiglitazone significantly ameliorates endothelial dysfunction indicated by asignificantly lower contractile re

11、sponse to PE and Ang II and enhancement of ACh-provoked relaxation in aortasisolated from diabetic rats5.PROTOCOLKinase Assay 1 cDNA encoding amino acids 174-475 of PPAR1 is amplified via polymerase chain reaction and inserted intobacterial expression vector pGEX-2T. GST-PPAR LBD is expressed in BL2

12、1(DE3)plysS cells and extracts. For saturationbinding analysis, bacterial extracts (100 g of protein) are incubated at 4C for 3 h in buffer containing 10 mM Tris(pH 8.0), 50 mM KCl, 10 mM dithiothreitol with 3H-BRL49653 (specific activity, 40 Ci/mmol) in the presence orabsence of unlabeled Rosiglita

13、zone. Bound is separated from free radioactivity by elution through 1-mL Sephadex G-25 desalting columns. Bound radioactivity eluted in the column void volume and is quantitated by liquid scintillationcounting1.MCE has not independently confirmed the accuracy of these methods. They are for reference

14、 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 Red O and photographedPage 2 of 3 www.MedChemE1.MCE has not independently confirme

15、d 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 measured and this day is regarded as day 0. Animals with a seru

16、mglucose level of 220-300 mg/dL are selected to be used in this study. Rats are randomly separated into five groupsfor daily drug administration for 8 weeks: group 1: control nondiabetic rats given a vehicle only (0.5 mL/kg of 0.5%carboxy methyl celleluse orally), group 2: control diabetic rats give

17、n a vehicle, group 3: diabetic rats receivingRosiglitazone (5 mg/kg orally), group 4: diabetic rats receiving losartan (2 mg/kg, orally), and group 5: diabetic ratsreceiving both Rosiglitazone and losartan2.MCE has not independently confirmed the accuracy of these methods. They are for reference onl

18、y.户使本产品发表的科研献 Br J Pharmacol. 2020 Jan 23. Free Radic Biol Med. 2018 Aug 21;126:259-268. Pharmacol Res. 2020 Jan 31;153:104679. Am J Cancer Res. 2020 Apr 1;10(4):1182-1193. J Cell Mol Med. 2019 Aug 23.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Lehmann JM, et al.

19、 An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J BiolChem. 1995 Jun 2;270(22):12953-6.2. Willson TM, et al. The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemicactivity of thiazolidinediones. J Med Chem. 1996 Feb 2;39(3):665-8.3. Thouennon E, et al. Rosiglitazone-activated PPAR induce