Vol 31, No 3 (2024)

Adagrasib is an orally bioavailable, highly selective, small-molecule, irreversible covalent inhibitor of KRASG12C. It was approved by the US FDA on December 12, 2022, for patients with tumors harboring the KRASG12C mutation in locally advanced or metastatic non-small cell lung cancer (NSCLC). Herein, synthesis, dosage and administration, mechanism of action, pharmacokinetics, pharmacodynamics, and adverse events of adagrasib are described.

High-density lipoproteins (HDL) have been shown to exert multiple cardioprotective and antidiabetic functions, such as their ability to promote cellular cholesterol efflux and their antioxidant, anti-inflammatory, and antiapoptotic properties. Type 2 diabetes (T2D) is usually associated with low high-density lipoprotein cholesterol (HDL-C) levels as well as with significant alterations in the HDL composition, thereby impairing its main functions. HDL dysfunction also negatively impacts both pancreatic β-cell function and skeletal muscle insulin sensitivity, perpetuating this adverse self-feeding cycle. The impairment of these pathways is partly dependent on cellular ATP-binding cassette transporter (ABC) A1-mediated efflux to lipid-poor apolipoprotein (apo) A-I in the extracellular space. In line with these findings, experimental interventions aimed at improving HDL functions, such as infusions of synthetic HDL or lipid-poor apoA-I, significantly improved glycemic control in T2D patients and experimental models of the disease. Cholesteryl ester transfer protein (CETP) inhibitors are specific drugs designed to increase HDLC and HDL functions. Posthoc analyses of large clinical trials with CETP inhibitors have demonstrated their potential anti-diabetic properties. Research on HDL functionality and HDL-based therapies could be a crucial step toward improved glycemic control in T2D subjects.

Tyrosine is an enzyme responsible for melanin production. Its abnormal accumulation in different parts of the body is known as hyperpigmentation. Tyrosinase inhibitors have been used as one of the main approaches to treat these kinds of cosmetic and medical issues. This review aimed to discuss the advances in patents for this class of inhibitors, focusing on synthetic ones, by studying recent patent applications (2012-2022). We performed a screening using the European Patent Office’s Espacenet database, from which 15 inventions were selected and fully studied. China has more patent applications, all of them were focused on synthetic methods and the majority declared at least two additional applications as antibrowning agents for fruits and vegetables, biological pesticides, and medicine to treat diseases like Parkinson’s or melanoma. The strategies employed by the investigators focused on the examination of previous literature, which oriented on the type of structures that have been found to show good inhibitory activity; the study also examined aspects of their reaction mechanisms and information about the structureactivity relationship. For some groups of inhibitors, such as benzaldehyde and anthraquinone derivatives, the data were meaningful and extensive. In contrast, arginyl and troponoids compounds were difficult to analyze due to the limited research works.

Metal-based coordination compounds have very special place in bioinorganic chemistry because of their different structural arrangements and significant application in medicine. Rapid progress in this field increasingly enables the targeted design and synthesis of metal-based pharmaceutical agents that fulfill valuable roles as diagnostic or therapeutic agents. Various coordination compounds have important biological functions, both those initially present in the body (endogenous) and those entering the organisms from the external environment (exogenous): vitamins, drugs, toxic substances, etc. In the therapeutic and diagnostic practice, both the essential for all living organisms and the trace metals are used in metal-containing coordination compounds. In the current review, the most important functional biologically active compounds were classified group by group according to the position of the elements in the periodic table.