Histone deacetylases (HDACs) are key epigenetic regulators involved in a variety of cancers, rendering them attractive therapeutic targets. Although several HDAC inhibitors have achieved clinical success, challenges such as poor isoform selectivity, acquired resistance, and off-target toxicity limit their broader application. Proteolysis-targeting chimeras (PROTACs) represent an innovative therapeutic strategy that enables ubiquitin-proteasome-mediated degradation of HDACs. This approach enhances specificity, overcomes resistance mechanisms, including those resulting from point mutations or persistent target activity, and enables sustained suppression at low concentrations, owing to its catalytic and event-driven mode of action. This review summarizes the structural classification and biological functions of HDACs and surveys recent advances in the design of HDAC-directed PROTACs. Key emphasis is placed on rational warhead selection, linker optimization, and the strategic choice of E3 ligase recruiters to guide degradation efficiency and isoform specificity. Representative degraders are evaluated for their pharmacological characteristics and antitumor efficacy across diverse malignancies. Current challenges and future directions for the development of HDAC degraders as clinically viable agents are also discussed.

Sirtuin 2 (SIRT2) is an NAD⁺-dependent lysine deacylase that is a member of the sirtuin enzyme family and plays essential roles in cytoskeletal regulation, chromatin remodeling, metabolic control, inflammation, neurodegeneration, and cancer progression. Its diverse biological functions have positioned SIRT2 as a compelling but challenging therapeutic target. This review provides an integrated overview of recent advances in SIRT2 structural biology, emphasizing the catalytic core, substrate-binding channel, and the inducible selectivity pocket that enables isoform discrimination. We summarize the medicinal chemistry landscape of classical SIRT2 inhibitors, highlighting major scaffolds and determinants of potency and selectivity. Emerging strategies based on targeted protein degradation-including SirReal-derived PROTACs, hydrophobic-tag degraders, and non-CRBN E3 ligase systems-are discussed in comparison with traditional occupancy-driven inhibition, underscoring the advantages of event-driven degradation for eliminating both catalytic and non-catalytic SIRT2 functions. Drug repurposing efforts and computational screening approaches further expand the repertoire of potential SIRT2 modulators. Finally, we outline current challenges and future directions, including the need for improved selectivity, better pharmacokinetic profiles, deeper mechanistic understanding, and development of chemical probes for underexplored sirtuin isoforms. Together, these advances highlight the rapidly evolving landscape of SIRT2-targeted therapeutics and their emerging potential in oncology, neurodegeneration, and metabolic disease.

Respiratory syncytial virus (RSV) is a common virus that causes respiratory infections, posing a serious threat, particularly to infants, the elderly, and individuals with compromised immune systems. As the leading cause of lower respiratory tract infections (LRTIs) in infants, RSV is responsible for millions of cases worldwide each year. Its incidence rises significantly during the winter influenza season. Despite decades of research, no effective vaccine exists, and antiviral treatment options remain limited, presenting a major challenge to global public health. With the advancement of emerging technologies, researchers have made significant progress in understanding the pathological and biological characteristics of RSV, the mechanisms of immune response, and its long-term health impacts. This review aims to provide a comprehensive overview of the basic biological characteristics, epidemiology, clinical manifestations, and diagnostic and therapeutic strategies of RSV and to explore preventive measures and future research directions, offering the latest scientific evidence for RSV prevention and control.

Arginine is critical in biosynthesis, energy generation, cell proliferation, and immune regulation. In the tumor microenvironment (TME), due to limited supply and high consumption, the competition for arginine is extremely fierce. It always ends up with the victory of tumor cells and immunosuppressive cells, which leads to the arginine deficiency for anti-tumor immune cells, resulting in immune tolerance of tumors. Therapies based on arginine metabolism have been extensively studied. An arginine deprivation therapy has been developed as the tumor progression relies on arginine support. To reverse the arginine shortage of anti-tumor immune cells in TME, supplying arginine to enhance immune therapy has been proposed. Achieving the optimal antitumor effects of these two opposed therapies requires a better understanding of arginine metabolism in TME. In this review, we compared the transport, synthesis, and metabolism of arginine in tumor cells and various immune cells, and proposed key processes that may serve as potential therapeutic targets. In addition, for the two therapies for arginine, deprivation and supplementation, the recent research of them was discussed, and the relevant clinical trials were collected and summarized, which might provide reliable references for the further study and application of arginine-based therapies.

Aims and Scope:The journal publishes timely critical reviews of topics related to medicinal research, broadly defined, to which the authors have made significant contributions.Appropriate topics include, but are not limited to, the underlying pathophysiology of important diseases and disease vectors; therapeutic approaches to the treatment of various diseases; the properties of molecular targets for therapeutic agents; important new methodologies facilitating the search for therapies; genomics and proteomics; structure-activity correlations of drug series; the development of new imaging and diagnostic tools; drug metabolism; drug delivery; and chemical, pharmacological, pharmacokinetic, pharmacodynamic, and clinical characteristics of important drugs.Articles are mainly solicited by the editors; however, voluntary contributions are also encouraged.In the latter case, potential authors are asked to contact the Editor-in-Chief with an outline before beginning to write in order to avoid duplication of effort and to ensure suitability of the topic and the level of coverage.

Transient receptor potential canonical (TRPC) channels, a subfamily of calcium-permeable cation channels, regulate diverse physiological processes and are implicated in disorders including neurological conditions, cardiovascular diseases, and chronic kidney disease. Recent advances in cryo-electron microscopy (cryo-EM) have elucidated TRPC structures, while subtype-selective modulators have clarified their pathophysiological roles and therapeutic potential. This review integrates the structural and functional attributes of TRPC channels, emphasizing their contributions to health and disease. We highlight synthetic strategies and structure-activity relationships driving the development of selective pharmacological tools, several of which show preclinical promise. By uniting TRPC biology with medicinal chemistry, this study provides strategic guidance for advancing clinically viable TRPC-targeted therapeutics.

The sulfanilamido skeleton is the core part of many clinical drugs with the para-aminobenzenesulfamido scaffold. Especially as the first type of synthetic antibacterial drugs, sulfanilamides have played important roles in preventing and treating infectious diseases for more than 90 years. Increasing efforts have been contributing toward the sulfanilamido skeleton with the incorporation of various unique substituents through medicinal design, which accessed great achievements that have not only broken the classical structure-activity relationship of antibacterial sulfanilamides, but also extended the other medicinal applications of sulfanilamides except for antibacterial drugs. Recently, the sulfanilamido-based medicinal design and research are becoming increasingly active, which have aroused widespread concern in the medicinal community. Thus, based on our work on sulfanilamido skeleton, this review article encompasses a robust collection of 746 references from 2008 to the present and, for the first time, provides comprehensive insights into sulfanilamido-based medicinal design and research across a wide range of medicinal potential. It is involved in antibacterial, antifungal, antitubercular, antiviral, anticancer, anti-inflammatory, antiglaucoma, antiparasitic, psychotherapeutic, antidiabetic, and other medicinal aspects. It also covers a large amount of sulfanilamido-based rich information on medicinal chemistry, including some important clinical sulfanilamido-based drugs, sulfanilamido-based medicinal molecular design strategies, structure-activity relationships, some important action targets, some important action mechanisms, as well as a multitargeting medicinal design strategy and medicinal chemicobiology. The foreseeable future research directions and trends toward medicinal design and development of sulfanilamido skeleton are prospected. This work might provide beneficial help for sulfanilamido-based rational design and development to afford sulfanilamido-based drugs with broad spectrum, high biological activity, and low toxicity to treat various diseases worldwide.

ABSTRACTMolecular imprinting is a very powerful tool in life science. The research areas benefiting from a wide range of capabilities of molecularly imprinted polymeric nanoparticles (nanoMIPs) include sample preparation, extraction, sensing/detection, diagnostics, and drug delivery. Recently, a new member of this family—therapy/control of cellular reactions—has arrived. Within this newest field, so far, the design and synthesis of very selective enzymatic inhibitors/activators have been described. Since enzymes act as catalysts of biochemical reactions, nanoMIPs pose enormous potential in managing biological processes. Furthermore, in recent years, articles focused on influencing cellular pathways by either interaction with cell surface receptors or by inactivation of signal molecules have begun to appear. This strategy opens a new perspective for nanoMIPs application—as selective, inexpensive, and stable therapeutics. However, there are still a lot of questions to be answered and many issues that must be addressed before the practical implementation of nanoMIPs in the therapeutic area. Among the main challenges belong safety, biodegradability, biodistribution, and clearance of nanoMIPs from the organism as well as their reproducible large‐scale production in accordance with quality control. This review aims to summarize the progress in nanoMIPs development enabling them to overcome main issues and increasing their competitiveness in the therapeutic area.