包装 | 价格(元) |
10mM (in 1mL DMSO) | 电议 |
5mg | 电议 |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
Cell experiment: | HUVECs are maintained in EGM2 media at 37℃ and 5% CO2. HUVECs or peritoneal macrophages are treated with vehicle or PF-06260933 in vitro to determine whether pharmacological inhibition of MAP4K4 alteres MAPK signalling in response to TNF-α[2]. |
Animal experiment: | Compound PF-06260933 (10 mg/kg, dissolved in dH2O) is orally administered to 8 to 10-week-old male Apoe-/- mice twice daily for 6 weeks. Ldlr-/- male mice are placed on high-fat diet (HFD) for 10 weeks before drug administration. Compound PF-06260933 is administered to male 8 to 10-week-old Ldlr-/- mice as above for 10 weeks. Oral administration of water is used as vehicle control in all studies. Mice are euthanized by CO2 inhalation followed by bilateral pneumothorax[2]. |
产品描述 | PF-06260933 is a highly selective small-molecule inhibitor of MAP4K4 with IC50s of 3.7 and 160 nM for kinase and cell, respectively. PF-06260933 treatment of human aortic endothelial cell (EC) robustly prevents TNF-α-mediated endothelial permeability in vitro, similar to MAP4K4 knockdown[2]. In the mice model, PF-06260933 treatment does not alter plasma lipid content, although reductions in glucose 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 this animal model (46.0% versus 25.5%), and a reduction in plasma glucose as well as lipid content is also observed[2]. [1]. Ammirati M, et al. Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment. ACS Med Chem 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 Dec 21;6:8995. |