Discovery of prolyl hydroxylase 2 inhibitors with new chemical scaffolds as in vivo active erythropoietin inducers through a combined virtual screening strategy.

Hypoxia-inducible factor (HIF) is identified to be a promising target to mediate the response to hypoxia. Its stability and activation are negatively controlled by prolyl hydroxylase 2 (PHD2). Thus, PHD2 inhibition has been perceived as a promising anti-anemia therapy. In this study, we carried out a structure-based virtual screening followed by in vitro and in vivo biological validation, with the goal to identify novel PHD2 inhibitors. As a result, a set of hits with new chemical scaffolds were revealed to be active in vitro for PHD2 inhibition. Compounds 2 and 3 were revealed to be capable of stabilizing HIF-α and stimulating erythropoietin (EPO) expression in cell-based assays. Notably, further in vivo assays revealed that 2 was capable of elevating the EPO plasma levels in C57BL/6 mice model. These findings provide new chemical scaffolds for further development of PHD2 inhibitors.

Influence of calcination temperature on the performance of Pd-Mn/SiO2-Al2O3 catalysts for ozone decomposition.

The catalytic decomposition of ozone was investigated over Pd-Mn/SiO(2)-Al(2)O(3) catalysts in the ground air. The catalysts were prepared by incipient wetness impregnation method and characterized by powder X-ray diffraction (XRD), thermo gravimetric (TG) analysis, and N(2) adsorption/desorption measurements (Brunauer-Emmet-Teller method). The influence of calcination temperature on the catalytic activities, and the lifetime test of the catalyst pretreated at 350 degrees C had been studied. XRD and TG results show that when calcined in the temperature range of 300-450 degrees C, manganese carbonate (MnCO(3)) is partly decomposed to MnOx (x=1.6-2.0) species in the catalysts. However, when calcined at 500 degrees C, MnOx partly turns into Mn(2)O(3) in the catalyst. The catalytic activity test indicates that the catalysts calcined at 300-400 degrees C exhibit the best performance for O(3) decomposition, and the completely conversion temperature of ozone (T(100)) is in the region of 30-35 degrees C, which is lower than surface temperature of water tanks of running automobile. Under gas hour space velocity (GHSV) of 635,000h(-1) and reaction temperature of 40 degrees C, after lifetime test for 80 h, the catalyst calcined at 350 degrees C keeps 90% conversion, which indicates that they have excellent ability to resist deactivation. The catalysts calcined at 300-400 degrees C show great potential to be applied at lower temperature, especially in winter and at the stage of automobile engine cold start.