XEN445 是一种内皮脂肪酶抑制剂(IC50:0.237 uM)，具有显著的ADME和PK活性，可以增强小鼠血浆中高密度脂蛋白胆固醇浓度。

XEN445, a potent and selective endothelial lipase(EL) inhibitor (IC50=0.237 uM), exhibitis good ADME and PK properties.

XEN445 exhibits good specificity over LPL and HL, and great inhibition activity against EL.

In vitro PI3K lipid kinase assay: (1) For PI3Kγ: human PI3Kγ (100 ng) is incubated at RT with kinase buffer (10 mM MgCl2, 1 mM β-glycerophosphate, 1 mM DTT, 0.1 mM Na3VO4, 0.1% Na Cholate and 15 μM ATP/100 nCi γ[33P]ATP, final concentrations) and lipid vesicles containing 18 μM PtdIns and 250 μM of PtdSer (final concentrations), in the presence of AS-605240 or DMSO. Kinase reaction is stopped by adding 250 μg of Neomycin-coated Scintillation Proximity Assay (SPA) beads. (2) For PI3Kα, β, and δ: varying amounts of ATP are incubated with the different purified PI3K isoforms and saturating concentrations of PtdIns. Consequently, IC50 determinations with PI3Kα, β, and δ, to evaluate inhibitor selectivity are performed as follows: 60 ng of PI3Kα are incubated at RT with kinase buffer, as described for PI3Kγ (but containing 89 μM ATP/300 nCi γ[33P]ATP and no Na Cholate, instead) and lipid vesicles containing 212 μM PtdIns and 58 μM of PtdSer. 100 ng of PI3Kβ are incubated at RT with kinase buffer (containing 70 μM ATP/300 nCi γ[33P]ATP, 4 mM MgCl2 and no Na Cholate) and lipid vesicles containing 225 μM PtdIns and 45 μM of PtdSer. 90 ng of PI3Kδ are incubated with kinase buffer (containing 65 μM ATP/300 nCi γ[33P]ATP, 1 mM MgCl2, and no Na Cholate) and lipid vesicles containing 100 μM PtdIns and 170 μM of PtdSer. The reactions are stopped after 2 hours.

1515856-92-4

C18H17F3N2O3

366.34

2-[(3S)-3-(2-吡啶基甲氧基)-1-吡咯烷基]-5-(三氟甲基)苯甲酸;XEN 445;XEN-445

Ethanol:36.6 mg/mL (100 mM)
DMSO:36.6 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years