Lipid nanoparticle-based mRNA delivery systems for cancer immunotherapy.

Cancer immunotherapy, which harnesses the power of the immune system, has shown immense promise in the fight against malignancies. Messenger RNA (mRNA) stands as a versatile instrument in this context, with its capacity to encode tumor-associated antigens (TAAs), immune cell receptors, cytokines, and antibodies. Nevertheless, the inherent structural instability of mRNA requires the development of effective delivery systems. Lipid nanoparticles (LNPs) have emerged as significant candidates for mRNA delivery in cancer immunotherapy, providing both protection to the mRNA and enhanced intracellular delivery efficiency. In this review, we offer a comprehensive summary of the recent advancements in LNP-based mRNA delivery systems, with a focus on strategies for optimizing the design and delivery of mRNA-encoded therapeutics in cancer treatment. Furthermore, we delve into the challenges encountered in this field and contemplate future perspectives, aiming to improve the safety and efficacy of LNP-based mRNA cancer immunotherapies.

Discovery of novel 2-[2-(3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetamide derivatives as HIF prolyl 4-hydroxylase inhibitors; SAR, synthesis and modeling evaluation.

The design, synthesis, and capacity to inhibit HIF prolyl 4-hydroxylases (PHDs) are described for 2-[2-(3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetamide analogs. These analogs revealed two kinds of novel scaffolds as PHD2 inhibitors. Synthetic routes were developed for the preparation of their analogs containing the new scaffolds. In addition, the structure-activity relationship (SAR) of the 2-[2-(3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetamide derivatives and their biological activities were reported. The complex structure of compound 18 with PHD2 was also obtained for the purpose of more efficient lead optimization.

Pd(II)-catalyzed decarboxylative acylation of phenylacetamides with α-oxocarboxylic acids via C-H bond activation.

A palladium-catalyzed decarboxylative acylation of phenylacetamides with α-oxocarboxylic acids via C-H bond activation is described. This protocol provides efficient access to a range of ortho-acyl phenylacetamides, which can be easily converted to 3-isochromanone derivatives.

Stereoselective amination of chiral benzylic ethers using chlorosulfonyl isocyanate: total synthesis of (+)-sertraline.

The stereoselective amination of various chiral benzylic ethers using chlorosulfonyl isocyanate is developed, and the application of this method to the total synthesis of a potent antidepressant, (+)-sertraline, from readily available 1-naphthol is also described.