PF-06260933 - MAP4K 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPF-06260933Cat. No.: HY-19562CAS No.: 1811510-56-1分式: CHClN分量: 296.75作靶點(diǎn): MAP4K作通路: MAPK/ERK Pathway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) DMSO : 30 mg/mL (101.10 mM; Need ultrasonic and

2、warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 3.3698 mL 16.8492 mL 33.6984 mL5 mM 0.6740 mL 3.3698 mL 6.7397 mL10 mM 0.3370 mL 1.6849 mL 3.3698 mL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 PF-06260933種度選擇性的 MAP4K4 分抑制劑，在激酶實(shí)驗(yàn)和細(xì)胞實(shí)驗(yàn)中的 IC50 值分別為 3.7 和160 nM。IC50 & Ta

3、rget MAP4K43.7 nM (IC50)體外研究PF-06260933 treatment of human aortic endothelial cell (EC) robustly prevents TNF-mediated endothelial1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEpermeability in vitro, similar to MAP4K4 knockdown 2.體內(nèi)研究 In the mice model, PF-06260933 treatment does not alter plasma

4、lipid content, although reductions inglucose levels are observed, which is consistent with whole-body-inducible Map4k4 knockout animals. PF-06260933 administration ameliorates further plaque development and/or promotes plaque regression in thisanimal model (46.0% versus 25.5%), and a reduction in pl

5、asma glucose as well as lipid content is alsoobserved 2.PROTOCOLCell Assay 2 HUVECs are maintained in EGM2 media at 37C and 5% CO2. HUVECs or peritoneal macrophages aretreated with vehicle or PF-06260933 in vitro to determine whether pharmacological inhibition of MAP4K4alteres MAPK signalling in res

6、ponse to TNF- 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Compound PF-06260933 (10mg/kg, dissolved in dH2O) is orally administered to 8 to 10-week-old maleAdministration 2 Apoe-/- mice twice daily for 6 weeks. Ldlr-/- male mice are placed o

7、n high-fat diet (HFD) for 10 weeks beforedrug administration. Compound PF-06260933 is administered to male 8 to 10-week-old Ldlr-/- mice as abovefor 10 weeks. Oral administration of water is used as vehicle control in all studies. Mice are euthanized byCO2 inhalation followed by bilateral pneumothor

8、ax 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Ammirati M, et al. Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment. ACS MedChem Lett. 2015 Oct 6;6(11):1128-33.2. Roth Flach RJ, et al. Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis. Nat Commun. 2015 Dec21;6:8995.McePdfHeightCaution: Product has not been fully validated for medical applic