Research progress in histone lysine demethylases inhibitors / 药学学报

The methylation of histone lysine plays a pivotal role in epigenetic regulation of gene expression. Histone lysine methylation modifications have 5 sites within histone H3(K4, K9, K27, K36, K79)and 1 site within histone H4(K20). Methylation at various sites has been shown to lead to transcriptional activation or silencing. Histone lysine methyltransferases(HKMTs)and histone lysine demethylases(HKDMs)collectively regulate the methylation modification state of histone lysine. It was reported that the mis-regulation of HKDMs is associated with the occurring and resistance of numerous malignant tumors, so more and more attention are received to HKDMs. Therefore, it is great significant in the study and development of HKDMs inhibitors. The inhibitors could be served not only as a tool in the investigation of the biological function, but also could be used as novel anti-cancer agents in the anticancer therapy. In this review, we provide a short summary of the HKDMs inhibitors recently reported and their potential in the treatment of diseases.

The feasibility of application of reverse docking method to the selectivity studies of protein kinase inhibitors / 药学学报

This investigation is to explore the feasibility of applying reverse docking method to the selectivity studies of protein kinase inhibitors. Firstly, a database that consists of 422 protein kinase structures was established through collecting the reported crystal structures or homology modeling. Then a reverse docking based method of protein kinase target screening was established, followed by the optimization of related parameters and scoring functions. Finally, seven typical selective kinase inhibitors were used to test the established method. The results show that the selective targets of these inhibitors have relatively high scoring function values (ranking in the first 35% of the tested kinase targets according to the scoring function values). This implies that the reverse docking method can be applied to the virtual screening of kinase targets and further to the selectivity studies of protein kinase inhibitors.

Effects of chloroquine diphosphate on proliferation and apoptosis of human leukemic K562 cells / 中国实验血液学杂志

The purpose of this study was to investigate the effects of chloroquine diphosphate on the proliferation and apoptosis of human leukemic K562 cells, and to elucidate its possible mechanism of activity. The inhibitory effect of chloroquine diphosphate with different concentrations on K562 cell proliferation was detected by MTT method. Apoptosis was measured by flow cytometry (FCM); morphological analysis of apoptosis was performed after staining with propidium iodide (PI) under fluorescence microscope; cell apoptosis was assessed by the DNA ladder shown agarose gel electrophoresis. After treatment with chloroquine diphosphate, K562 cells were stained by Rhodamine 123 to detect changes in mitochondrial transmembrane potential (DeltaPsim) by FCM. The results showed that the cell viability decreased in dose-dependent manner, following chloroquine diphosphate treatment at different concentrations (1.5625, 3.125, 6.25, 12.5, 25, 50 and 100 micromol/L) for 24, 48 and 72 hours. By FCM analysis, the significant increases of sub-G(1) were observed. DNA ladder was detected and apoptotic nuclei were observed. DeltaPsim decreased in K562 cells after chloroquine diphosphate treatment. It is concluded that the chloroquine diphosphate can inhibit the proliferation of K562 cells and induce cell apoptosis, which may relate to down-regulation of mitochondrial transmembrane potential (DeltaPsim).

Progress in the design of selective ATP-competitive kinase inhibitors / 药学学报

Kinases play crucial roles in the life of cell. Their functional abnormity usually leads to many human major diseases including tumors. The prospecting of ATP-competitive small-molecule kinase inhibitors targeting kinases of therapeutic interest has become the focus of researches. Due to the high conservation of the catalytic domain of kinases, the selectivity of kinase inhibitors is poor in general. However, along with the development of structural biology and computer-aided drug design, great progress in the research of selective, ATP-competitive kinase inhibitors has been achieved in recent years. In this account, the review has been made on the development of the design of selective kinase inhibitors.

A Review on Relations Between Pathogenicity and Melanin of Plant Fungi / 微生物学通报

Melanin is formed by oxidative polymerization of phenolic compounds,basically different kinds of melanin come from different organisms.DOPA melanin and DHN melanin have same physical and chemical characters although they have different biosynthetic pathway.DHN melanin is common in plant fungi and plays an important role on infection.The melanin accumulates in the fungal cell walls and prevents organic and inorganic molecules penetrating out,that insures appressorium's pressure and infection ability.This paper has reviewed the kinds and characters,especially discussed the role of melanin during pathogen infection based on our some research.