Search results for: Shilong Li

Authors: Changde Zhang, Qiang Zhang, Shilong Zheng, Jiawang Liu, Shanchun Guo, Qiu Zhong, Guangdi Wang

Abstract:

Fulvestrant was approved by FDA to treat breast cancer as a selective estrogen receptor downregulator (SERD) with intramuscular injection administration. ZB716, a fulvestarnt-3 boronic acid, is an SERD with comparable anticancer effect to fulvestrant, but could produce good pharmacokinetic properties under oral administration with mice or rat models. To understand why ZB716 produced much better oral bioavailability, it was proposed that the boronic acid blocked the phase II direct biotransformation with the hydroxyl group on the 3 position of the aromatic ring on fulvestrant. In this study, ZB716 or fulvestrant was incubated with human liver microsome and oxidation cofactor NADPH in vitro. Their metabolites after oxidation were profiled with the Q-Exactive, a high-resolution mass spectrometer. The result showed that ZB716 blocked the forming of hydroxyl groups on its benzene ring except for the oxidation of C-B bond forming fulvestrant in its metabolites, and the concentration of fulvestrant with one more hydroxyl group found in the metabolites from incubation with fulvestrant was about 34 fold high as that formed from incubation with ZB716. Compared to fulvestrant, ZB716 is expected to be much difficult to be further bio-transformed into more hydrophilic compounds, to be difficult excreted out of blood system, and to have longer residence time in blood, which can lead to higher oral bioavailability. This study provided evidence to explain the high bioavailability of ZB716 after oral administration from the perspective of its difficulty of oxidation, a phase I biotransformation, on positions on its aromatic ring.

Keywords: biotransformation, fulvestrant, metabolite profiling, ZB716

Procedia PDF Downloads 225

Authors: Runlin Liu, Shilong Li

Abstract:

China is a mountainous country, with two-thirds of its territory covered by plateaus, hills, and mountains, and nearly half of the cities and towns are distributed in mountainous areas. Compared with the environmental constraints in the development path of cities and towns in the plains, there are heterogeneities in aspects such as spatial characteristics, growth mode, and ecological protection and so on for mountain village and townlets, and the development path of mountain village and townlets has a bidirectional relationship between mountain space and economic growth. Based on classical growth theory, this article explores the two-dimensional coupling relation between space and economy in mountain village and townlets under background of rural rejuvenation. GIS technology is adopted in the study to analyze spatial trends and patterns, economical spatial differentiation characteristics of village and townlets. This powerful tool can also help differentiate and analyze limiting factors and assessment systems in the economic growth of village and townlets under spatial dimension of mountainous space. To make the research more specific, this article selects mountain village and townlets in Southwest China as the object of study; this provides good cases for analyzing parallel coupling mechanism of the duality structure system between economic growth and spatial expansion and discussing the path selection of spatial economic growth of mountain village and towns with multiple constraints. The research results can provide quantitative references for the spatial and economic development paths of mountain villages and towns, which is helpful in realizing efficient and high-quality development mode with equal emphasis on spatial and economic benefits for these type of towns.

Keywords: coupling mechanism, geographic information technology, mountainous town, synergetic development, spatial economy

Procedia PDF Downloads 103