Showing papers by "Yi-Chao Zheng published in 2015"

A Systematic Review of Histone Lysine-Specific Demethylase 1 and Its Inhibitors.

Abstract: Histone lysine-specific demethylase 1 (LSD1) is the first discovered and reported histone demethylase by Dr. Shi Yang's group in 2004. It is classified as a member of amine oxidase superfamily, the common feature of which is using the flavin adenine dinucleotide (FAD) as its cofactor. Since it is located in cell nucleus and acts as a histone methylation eraser, LSD1 specifically removes mono- or dimethylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) through formaldehyde-generating oxidation. It has been indicated that LSD1 and its downstream targets are involved in a wide range of biological courses, including embryonic development and tumor-cell growth and metastasis. LSD1 has been reported to be overexpressed in variety of tumors. Inactivating LSD1 or downregulating its expression inhibits cancer-cell development. LSD1 targeting inhibitors may represent a new insight in anticancer drug discovery. This review summarizes recent studies about LSD1 and mainly focuses on the basic physiological function of LSD1 and its involved mechanisms in pathophysiologic conditions, as well as the development of LSD1 inhibitors as potential anticancer therapeutic agents.

Design, Synthesis, and Structure–Activity Relationship of Novel LSD1 Inhibitors Based on Pyrimidine–Thiourea Hybrids As Potent, Orally Active Antitumor Agents

Abstract: Histone lysine specific demethylase 1 (LSD1) was reported to be overexpressed in several human cancers and recognized as a promising anticancer drug target. In the current study, we designed and synthesized a novel series of pyrimidine–thiourea hybrids and evaluated their potential LSD1 inhibitory effect. One of the compounds, 6b, containing a terminal alkyne appendage, was shown to be the most potent and selective LSD1 inhibitor in vitro and exhibited strong cytotoxicity against LSD1 overexpressed gastric cancer cells. Compound 6b also showed marked inhibition of cell migration and invasion as well as significant in vivo tumor suppressing and antimetastasis role, without significant side effects by oral administration. Our findings indicate that the pyrimidine–thiourea-based LSD1 inactivator may serve as a leading compound targeting LSD1 overexpressed cancers.

Elastin-like polypeptides (ELP) for prokaryotic expression of fusion protein Prx by non-digestion and non-chromatography purifying method

Abstract: The invention discloses elastin-like polypeptides (ELP) for prokaryotic expression of fusion protein Prx by a non-digestion and non-chromatography purifying method and belongs to the field of genetic engineering. According to the elastin-like polypeptides, the type of the fourth amino acid in an elastin-like pentapeptide unit is changed and the elasticity function of the fourth amino acid is improved, and therefore, the reduction of the ELP length becomes possible. The ratio of K, V and F in the fourth basic group in the ELP pentapeptide unit is enabled to be 1: 6: 3. In terms of inteins, the high-efficiency intein gp41-1 is adopted; the C-terminal and the N-terminal of the intein are expressed separately, and the internal gene of the intein is mutated. The elastin-like polypeptides (ELPs) are ELP-IN and precursor protein ELP-IC-PrxI. The protein Prx is purified in a non-chromatography way by use of the elasticity function of the elastin-like polypeptides; no chromatographic column is required for separation, and the target protein precipitates by virtue of incubation at a certain temperature; besides, the precipitate can be re-dissolved in a buffer solution, and consequently, the protein can be purified more efficiently and quickly.