The development of small-molecule inhibitors targeting MYC / 药学学报

The MYC gene, one of the most common dysregulated driver genes in human cancers, is composed of three paralogous genes C-MYC, N-MYC and L-MYC. It is abnormally activated in more than half of cancer types. Since MYC plays an important role in the formation, maintenance and progression of cancer, targeting MYC is an effective strategy for cancer treatment. As a potential anti-cancer target, MYC is considered "undruggable" because it lacks a suitable pocket for accommodating small molecule inhibitors. Recently, under the guidance of protein structure information and many computational tools, many indirect strategies to inhibit MYC have emerged and shown favorable anti-cancer effects in tumor models. In this paper, the recent small molecules that indirectly target MYC are divided into inhibitors acting on the protein-protein interaction (PPI) among MYC and other proteins, and targeting inhibitors regulating MYC action. Additionally, the introduction and assessment towards compounds with different mechanisms are summarized to provide reference for the further research of MYC inhibitors.

Metacercarial proteins interacting with WD40-repeat protein of Clonorchis sinensis

The WD40-repeat proteins serve as a platform coordinating partner proteins and are involved in a range of regulatory cellular functions. A WD40-repeat protein (CsWD1) of Clonorchis sinensis previously cloned is expressed stage-specifically in the tegumental syncytium of C. sinensis metacercariae. In the present study, interacting proteins with the CsWD1 protein was purified by immunoprecipitation and 2 dimension gel electrophoresis from the C. sinensis metacercaria soluble extract, and tryptic peptides were analyzed by LC/ESI-MS. Putative partner proteins were annotated to be actin-2, glyceraldehyde-3-phosphate dehydrogenase, and hypothetical and unmanned proteins. The CsWD1 protein was predicted to contain 3 conserved actin-interacting residues on its functional surface. With these results, the CsWD1 protein is suggested to be an actin-interacting protein of C. sinensis.

Distribution Change of WD40 Repeat Protein 1 in Artificially Induced Senescent PC12 Cells

Background: WDR1 is thought to be correlating with polymerization and depolymerization of actin protein. Though WDR1 was found to be within nucleus, in which actin could not be present by previous studies, the exact distribution pattern of WDR1 protein under various circumstances was not elucidated up to the present time. In this regard, we tried to see a change in the distribution of WDR1 protein within artificially induced senescent PC 12 pheochromocytoma cells for the first time. Methods: PC12 pheochromocytoma cells (ATCC CRL-1721) were grown in the culture media including 1 micrometer 3'-Azido-3'-deoxythymidine (AZT, Sigma-Aldrich, USA). The senescence of the cells was confirmed by senescence detection kit (Calbiochem, San Diego, CA). Immunocytochemical study by using WDR1 antibody was also performed in the cells treated with AZT during 0, 75 and 153 days. Results: WDR1 protein was mainly observed within the cytoplasm of the cells not treated with AZT. However, the distribution of the same protein was changed into the nucleus after 153 day-AZT treatment. Conclusion: The distribution of WDR1 protein was changed into nucleus in the artificially senescent PC12 cells.