Ugi-reaction-derived ionizable lipids with cyclic tertiary amine heads enable spleen-targeted mRNA delivery.

Lipid nanoparticles (LNPs) have become an important platform for nucleic acid delivery. However, LNP-mediated delivery to non-hepatic organs and specific cell types remains a non-negligible challenge. As a key component of LNPs, ionizable lipids were rationally designed to adjust the LNPs properties to achieve organ-targeted delivery.

Design, synthesis, anticancer activity evaluation and molecular dynamics study of pyrazine N-oxide-based SHP2 allosteric inhibitors.

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2), the first oncoprotein identified in the protein phosphatase family, has emerged as a promising anticancer target in recent years. Here, we report the discovery of a novel series of pyrazine N-oxide derivatives as potent SHP2 allosteric inhibitors and the identification of compound C5 as a highly potent and selective SHP2 allosteric inhibitor (SHP2 IC = 0.023 μM, SHP2 IC = 0.

LC-MS untargeted metabolomics reveals metabolic disturbance and ferroptosis in MWCNTs-induced hepatotoxicity of Cyprinus carpio.

In recent years, there is a great concern about the potential adverse effects of carbon nanotubes (CNTs) on the aquatic systems due to their increasingly extensive application. In this study, juvenile Cyprinus carpio were exposed to multi-walled CNTs (MWCNTs) at concentrations of 0, 0.25, and 2.

Design, Synthesis, and Biological Evaluation of Proteolysis-Targeting Chimeras as Highly Selective and Efficient Degraders of Extracellular Signal-Regulated Kinase 5.

Extracellular signal-regulated kinase 5 (ERK5) is recognized as a key member of the mitogen-activated protein kinase family and is involved in tumor growth, migration, and angiogenesis. However, the results of ERK5 inhibition in multiple studies are controversial, and a highly specific ERK5-targeting agent is required to confirm physiological functions. Using proteolysis-targeting chimera technology, we designed the selective ERK5 degrader and examined its biological effect on cancer cells.