ABSTRACT
With high selectivity and potency, target protein degradation technology has recently emerged as a strategy for drug discovery and design. Proteolysis-targeting chimeras (PROTAC) function as inducers for the degradation of target proteins and are a research focus in drug development. Current research on PROTAC mainly revolves around the rational design of PROTAC molecules, the discovery of new E3 ubiquitin ligase ligands and improvement in drug targeting. In this review, we focus on the PROTAC linker and its effects on the generation of the E3 enzyme-PROTAC-target protein ternary complex from three standpoints: length, binding site and chemical properties. We discuss the influences of the linker on the efficacy and the selectivity of PROTAC molecules.
ABSTRACT
With the significant breakthrough that programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) antibody drugs achieved promising clinical outcomes across various tumor types, immunotherapy targeting immune checkpoint has been considered a promising way to treat cancer. However, most recently studies suggest that the hyperprogressive disease occurred frequently during the therapy of using PD-1/PD-L1 antibody drugs and has become an urgent problem to be solved. In this review, we summarize the progress and potential reasons of hyperprogressive disease caused by PD-1/PD-L1 blockade, and further discuss its application based on the rational use of biomarkers for searching the benefit patients.
ABSTRACT
<p><b>OBJECTIVE</b>To study the anti-hyperglycemic effect and its mechanism of Dendrobium candidum (DC).</p><p><b>METHOD</b>Normal mice, adrenaline-induced hyperglycemic mice, streptozotocin-induced diabetic (STZ-DM) rats were used. The mechanisms of the anti-hyperglycemic action were studied with radio-immunoassay, immunohistochemical HRP-SPA stain, etc.</p><p><b>RESULT</b>DC could not obviously decrease the serum glucose concentrations and insulin levels in normal mice. It could increase serum insulin levels and decrease serum glucagons concentrations in STZ-DM rats. The results of immunohistochemical stain demonstrated that the number of islet beta cells was increased and that of islet a cells was decreased in STZ-DM rats. It could also decrease the serum glucose concentrations and increase liver glucogen contents in adrenaline-induced hyperglycemic mice.</p><p><b>CONCLUSION</b>DC has obvious anti-hyperglycemic effects in adrenaline-induced hyperglycemic mice and STZ-DM rats. Its mechanisms are stimulating the secretion of insulin from beta cells and inhibiting the secretion of glucagons from a cells, and it can probably decrease the decomposition of liver glucogen and increase the synthesis of liver glucogen.</p>