PD-169316 _p38 MAPK 抑制剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPD 169316Cat. No.: HY-10578CAS No.: 152121-53-4分式: CHFNO分量: 360.34作靶点: p38 MAPK; Autophagy作通路: MAPK/ERK Pathway; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 12.5 mg/mL (34.69 m

2、M; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 1.25 mg/mL (3.47 mM); Suspended solution; Need ultrasonic2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.25 mg/mL (3.47 mM); Suspended solution; Need ultrasonic3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small

3、Molecules 您边的抑制剂师www.MedChemESolubility: 1.25 mg/mL (3.47 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 PD 169316种效，细胞透过的，有选择性的 p38 MAP kinase 抑制剂，IC50 值为 89 nM。IC50 & Target IC50: 89 nM (p38 MAPK) 5体外研究 PD169316 (10 M) inhibits TGF and Activin A, but not BMP4 signaling in CaOV3 cells. PD169316 (0.2-20

4、M) inhibits TGF-induced Smad2 nuclear translocation, Smad7 mRNA induction, and reporter gene activity inCaOV3 cells 1. PD169316 (10 M) shows a significantly increased rate of proliferation in Nestin knockdowncells, and can rescue the effect of Nestin knockdown on cell viability in the absence of EGF

5、 2. PD169316significantly inhibits p38 MAP kinase activity with no significant change in ERK activity in PC12 cells.PD169316 (10 M) blocks apoptosis induced by trophic factor withdrawal in differentiated PC12 cells 3.体内研究 PD169316 (30 ng/5 L) or in combination with U0126 improves spatial learning in

6、 MWM in A-injected rats,20 days after A-injection. Pretreatment with U0126 and PD169316 decreases the levels of phosphorylatedform of ERK and p38 to about 77.7 and 64.2%, respectively, and causes a significant increase in c-fos, p-CREB, NRF-1 and TFAM protein levels, compared to the A-injected group

7、 4.PROTOCOLKinase Assay 3 Sixteen hours after the removal of serum from Rat-1 fibroblasts or NGF from differentiated PC12 cells, thecells are incubated in the absence or presence of insulin (50 ng/mL) for 15 min at 37C. After washing with 2mL of ice-cold PBS, the cells are solubilized in 400 L of ic

8、e-cold immunoprecipitation buffer containing 10mM Tris, pH 7.4, 1% Triton X-100, 0.5% Nonidet P-40, 150 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.2 mMsodium orthovanadate, and 0.2 mM phenylmethylsulfonyl fluoride. The cell lysates are centrifuged to removeinsoluble material, and 200 g of the supernatant prot

9、ein (400 L, total volume) are incubated with 1 g ofanti-p38 antibodies for 1 h at 4C followed by incubation with 30 L of Protein G Plus/Protein A-agarose foran additional hour. The immunocomplexes are pelleted and washed twice in immunoprecipitation buffer andthen once in kinase ish buffer (50 mM -g

10、lycerolphosphate, 1 mM EGTA, 20 mM MgCl2, 100 M sodiumorthovanadate). The protein kinase assay is initiated by the addition of 20 L of 2 reaction buffer (50 mM-glycerolphosphate, 1 mM EGTA, 20 mM MgCl2, 100 M sodium orthovanadate, 0.1 mg/mL ATF-2 (N-terminal half), 50 g/mL IP20, a peptide inhibitor

11、of c-AMP dependent protein kinase, 200 M ATP, and 0.9mCi/mL 32PATP) to 20 L of immune complex. The reaction is allowed to proceed for 10 min at 30C andthen terminated by the addition of 2 LaemmLi sample buffer and analyzed by SDS-polyacrylamide gelelectrophoresis using 12% acrylamide gels. After ele

12、ctrophoresis, the gels are dried and subjected tophosphoimaging.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Adult male albino Wistar rats weighing 210-280 g are used in these experiments. Animals are divided into sixAdministration 4 groups: (

13、A) A-injected group, which receives bilateral intra-CA1 injection of A (30 ng/3 L PBS per side), 42/3 Master of Small Molecules 您边的抑制剂师www.MedChemEh after unilateral i.c.v. administration of DMSO (5 L/rat), without receiving any treatment; (B) vehicle group,which only receives carrier, DMSO in later

14、al ventricle and PBS (3 L/side) in both CA1 regions; (C) ERKinhibitor group, which receives i.c.v. infusion of U0126 (30 g/5 L 1% DMSO in PBS) with PBS injection (3 L/side in CA1); (D) p38 inhibitor group, which receives i.c.v. infusion of PD169316 (30 g/5 L 1% DMSO inPBS) with PBS injection (3 L/si

15、de in CA1); and (E) treatment group which receives i.c.v. administration ofU0126 (30 g/5 L 1% DMSO in PBS), 4 h prior to intra-hippocampal A (30 ng/3 L PBS per side) injection;(F) treatment group which receives i.c.v. administration of PD169316 (30 g/5 L 1% DMSO in PBS), 4 hprior to intra-hippocampa

16、l A (30 ng/3 L PBS per side) injection. The aforementioned groups enter twoexperimental protocols: behavioral experiments and molecular studies. All the groups of animals in molecularstudy are considered as 7 and 20-day experimental groups.MCE has not independently confirmed the accuracy of these me

17、thods. They are for reference only.户使本产品发表的科研献 Genes Dev. 2018 Sep 1;32(17-18):1215-1225. Oncol Rep. 2017 Dec;38(6):3668-3676. Virology. 2017 Aug;508:150-158. Int J Med Sci. 2016 Jul 18;13(8):611-9. Oncol Lett. 2018 Jan;15(1):235-242.See more customer validations on HYPERLINK / www.MedChemEREFERENCE

18、S1. Fu Y, et al. The p38 MAPK inhibitor, PD169316, inhibits transforming growth factor beta-induced Smad signaling in human ovariancancer cells. Biochem Biophys Res Commun. 2003 Oct 17;310(2):391-7.2. Hu W, et al. Suppression of Nestin reveals a critical role for p38-EGFR pathway in neural progenito

19、r cell proliferation. Oncotarget. 2016Dec 27;7(52):87052-87063.3. Kummer JL, et al. Apoptosis induced by withdrawal of trophic factors is mediated by p38 mitogen-activated protein kinase. J Biol Chem.1997 Aug 15;272(33):20490-4.4. PD 169316, et al. ERK and p38 inhibitors attenuate memory deficits and increase CREB phosphorylation and PGC-1 levels in A