ABSTRACT
The proteolysis targeting chimeras (PROTACs) technology has been rapidly developed since its birth in 2001, attracting rapidly growing attention of scientific institutes and pharmaceutical companies. At present, a variety of small molecule PROTACs have entered the clinical trial. However, as small molecule PROTACs flourish, non-small molecule PROTACs (NSM-PROTACs) such as peptide PROTACs, nucleic acid PROTACs and antibody PROTACs have also advanced considerably over recent years, exhibiting the unique characters beyond the small molecule PROTACs. Here, we briefly introduce the types of NSM-PROTACs, describe the advantages of NSM-PROTACs, and summarize the development of NSM-PROTACs so far in detail. We hope this article could not only provide useful insights into NSM-PROTACs, but also expand the research interest of NSM-PROTACs.
ABSTRACT
Immune metabolism is an emerging highlight in recent years.Revealing the metabolic characteristics of different immune cells in different responses may provide new perspective and direction for the pathogenesis and therapy of many immune-related diseases.Sepsis is a complex systemic inflammation caused by trauma,infection and other pathogenic factors.The immune cells have different metabolic features at different stages of the disease.These metabolic features are also involved in the regulation of immune cell proliferation,differentiation and function.By summarizing and analyzing the relevant literatures of immune cell metabolism and inflammation regulation in recent years,the metabolic regulatory factors of different immune cell subgroups and the related characteristics of immune cell metabolism in patients with sepsis were summarized.The in-depth understanding of the metabolic state in different immune cells,and the pathophysiological mechanism of septic immune disorders,especially the immune paralysis stage,would provide a theoretical basis for the clinical application of immune metabolic therapy.
ABSTRACT
A series of 5-amino-2-( benzylthio ) thiazole-4-carboxamide derivatives were designed and synthesized to discover novel compounds with anti-tumor activity. Compounds DDO-5401-DDO-5416 were synthesized using 2-amino-2-cyanoacetamide as the start material. The structures of the synthesized compounds were confirmed by IR, 1 H NMR and ESI-MS. The in vitro anti-tumor activities of the synthesized compounds were determined by MTT assay in HCT116 , HepG2 , A549 , MDA-MB-231 and MCF-7 cell lines. Target compounds showed good anti-tumor activity especially in A549 cell line. SAR study showed that electron donating groups were more favorable than electron absorption ones. Compound DDO-5413 exhibited noteworthy activity in MDA-MB-231 and MCF-7 cell lines with IC50 value lower than the positive reference dasatinib. It suggested that DDO-5413 might be the candidate for further investigation.
ABSTRACT
@#To obtain ARE-Nrf2 potent activators through modifying the structure of the lead compound CPUY191001. 17 compounds were synthesized by aldol condensation, their cytotoxicity were tested using MTT assay, and ARE inductivity of these target compounds were analyzed by luciferase reporter gene assay. The biological evaluation results showed that most synthesized chalcone derivatives nearly had no cytotoxicity, and compounds 2, 3, 10 conducted better activity and in concentration-dependent manner. Compounds 2, 3, 10 are potential agents in the development of anti-inflammatory and chemoprevention, suggesting that compounds 2, 3, 10 are worth for further investigation.