Discovery of novel protein degraders based on bioorthogonal reaction-driven intracellular self-assembly strategy.

Proteolysis targeting chimera (PROTAC) is a promising therapeutic modality capable of degrading undruggable proteins and overcoming the shortcomings of traditional inhibitors. However, the molecular weight and pharmaceutical properties of PROTACs fall outside of a reasonable range. To overcome the inherent poor druggability of PROTACs, an intracellular self-assembly strategy based on bio-orthogonal reaction was proposed and applied in this study.

Novel strategies and promising opportunities for targeted protein degradation: An innovative therapeutic approach to overcome cancer resistance.

Targeted Protein Degradation is an emerging and rapidly developing technique for designing and treating new drugs. With the emergence of a promising class of pharmaceutical molecules, Heterobifunctional Proteolysis-targeting chimeras (PROTACs), TPD has become a powerful tool to completely tackle pathogenic proteins with traditional small molecule inhibitors. However, the conventional PROTACs have gradually exposed potential disadvantages of poor oral bioavailability and pharmacokinetic (PK) and absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics due to their larger molecular weight and more complex structure than the conventional small-molecule inhibitors.

Design, synthesis and bioactivity evaluation of self-assembled PROTACs based on multi-target kinase inhibitors.

Proteolysis targeting chimera (PROTAC) is a heterobifunctional molecule with enormous potential for its ability to overcome the limitations of traditional inhibitors. However, its inherent disadvantages have been increasingly revealed, such as poor cell permeability caused by large molecule weight. Herein, to overcome the inherent shortcomings, intracellular self-assembly was proposed based on bioorthogonal reaction and molecular fragments, affording a novel type of self-assembled PROTACs.

Morality is Supreme: The Roles of Morality, Fairness and Group Identity in the Ultimatum Paradigm.

Purpose: A large number of decision-making need to be carried out in the context of social interactions. Previous studies have demonstrated the impact of fairness perception, moral judgment, and group identity on decision-making. However, there is no clear conclusion as to how the effect of these factors existing simultaneously on decision-making and the extent to which these factors play a role.

Disequilibrium in the CD8CD28/CD8CD28 T Lymphocyte Balance Is Related to Prognosis in Rats with Trinitrobenzenesulfonic Acid-Induced Colitis.

Purpose: The CD8CD28/CD8CD28 T lymphocyte balance is vital for human ulcerative colitis (UC) but has not been defined in experimental colitis. This investigation will try to identify the changes that occur in the CD8CD28/CD8CD28 T lymphocyte balance during the progression of trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats.

Methods: The frequencies of blood CD8CD28 and CD8CD28 T lymphocytes were detected in the rats belonging to the normal, model, and treated groups on five days using flow cytometry.