Medicinal Research Reviews最新文献

The burgeoning field of CBMs represents a significant stride in the evolution of targeted therapeutics. This class of compounds, characterized by their ability to form stable covalent bonds with specific proteins of interest (POIs) or biological effectors, has emerged as a promising avenue for addressing complex pathological conditions such as drug-resistant diseases, undruggable targets, and chronic disorders requiring sustained target modulation. The integration of covalent chemistry in molecular design allows for the creation of highly specific and potent agents capable of modulating protein function with unprecedented precision. Herein, we meticulously classify CBMs according to the object of covalent bond formation and provide a discussion of the progress of CBMs since 2001, covering the design principles, molecular composition, covalent properties, and their reaction efficiencies, which not only reveals the potential of CBMs in drug discovery, but also emphasizes the importance of achieving innovations and breakthroughs in this field.

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 dramatic surge in dengue cases in early 2024, endangering half the global population, urgently necessitates faster diagnostic methods. Nanotechnology-enabled optical biosensors offer a promising avenue, leveraging nanomaterial properties for highly sensitive detection of dengue virus (DENV), potentially surpassing conventional techniques in terms of simplicity, speed, and cost-effectiveness. This systematic review analyzes recent advancements in these biosensors for DENV diagnosis. Following PRISMA 2020 guidelines, we systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases (2010–June 1, 2025; OSF: https://osf.io/3gmey/). The methodological quality of the 98 included studies was assessed using a modified CASP checklist. Diverse nanotechnology-based optical biosensors were identified. SPR (36.7%) was the most common transducer, followed by fluorescence (24.5%), colorimetry (15.3%), and SERS (8.2%). Gold-based nanomaterials (35.7%) were most frequently employed, with silver nanomaterials (15.3%), quantum dots (15.3%), and graphene-based materials (15.3%) also showing promise. DENV NS1 protein was the primary target analyte (21.4%). Importantly, almost half of the studies (44.9%) used clinically relevant human samples. While many optical biosensors show promise, challenges hinder their demonstration of the true potential for point-of-care use in their current format; however, they offer high specificity and faster results, laying a strong foundation for cost-effective clinical diagnostics. Nanotechnology-driven optical biosensors offer a transformative approach for DENV detection. Advances in computational design and green synthesis of novel nanomaterials are key to addressing stability and field-deployment challenges. These innovations are crucial for developing robust, sensitive, and user-friendly tools to manage dengue and improve patient outcomes globally.

The monkeypox (mpox) outbreak has once again become a Public Health Emergency of International Concern, increasing the focus of research on the development of anti-monkeypox drugs. Monkeypox virus (MPXV) is a member of the Orthopxviridae genus, which also contains the variola virus, cowpox virus, and vaccinia virus. As no specific drugs for mpox are available, tecovirimat and brincidofovir for the treatment of smallpox infection are recommended to treat Mpox infection. The purpose of this review is to provide reference for further development of Mpox virus antiviral drugs by summarizing the resolving Mpox virus target protein structures and its mechanism of action, drugs with potential anti-Mpox virus activity, in vitro and in vivo inhibitory activity detection methods of anti-Mpox virus drugs, and the prevention of drug resistance. We hope to facilitate the discovery of antiviral drugs for MPXV by providing insights into the further development of appropriate anti-Mpox drugs based on currently available viral protein targets.

Alzheimer's disease (AD) is a common progressive neurodegenerative disease characterized by abnormal deposition of amyloid-β protein (Aβ) and the formation of neurofibrillary tangles (NFT). Although there are drugs available for clinical treatment, they do not fundamentally cure AD, so early diagnosis and intervention for AD are essential. In recent years, near-infrared fluorescent (NIRF) probes have been widely used in diagnosing AD due to their advantages of high tissue penetration, low autofluorescence interference, and non-invasiveness. This paper reviewed the recent progress of NIRF probes in AD. We described the effects of NIRF probes on AD biomarkers, including Aβ protein, Tau tangles, mitochondrial viscosity, reactive oxygen species, copper ions, zinc ions, and so on. In detail, we also described the optical properties, in vitro detection, and in vivo imaging of NIRF probes based on different dyes and their derivatives, such as curcumin, Boron dipyrromethene, Quinoline, and Donor-Acceptor. Despite significant progress, NIRF probes remain challenging in imaging and treating AD in vivo. Their selectivity and sensitivity need to be improved due to the complex structure of brain tissue and interfering factors. In conclusion, studying NIRF probes provides us with new ideas. Through further optimization, these probes may be used for early diagnosis and treatment detection of AD to better cope with the challenges brought by AD.

The absence of suitable biological targets is one of the most formidable obstacles to drug development. The investigation of “undruggable” proteins has the potential to significantly increase the druggable proteome. Cryptic pockets represent specific potential pockets that provide a rare opportunity to target “undruggable” proteins. The identification of cryptic pockets, in combination with drug design studies, has made significant progress, especially due to the emergence of artificial intelligence (AI) technology. However, there has been no comprehensive review of the methods and successful identification of cryptic pockets and associated inhibitors for “undruggable” targets. Here, we systematically summarize and analyze the latest strategies for identifying cryptic pockets and designing related inhibitors. First, we analyze both computational methods and experimental approaches for the discovery of cryptic pockets or regions. We will also discuss studies that have successfully identified specific cryptic pockets and developed compounds that inhibit the “undruggable” targets, using these as successful case studies. The limitations, drawbacks, and underlying trends in cryptic pocket identification and inhibitor design will also be discussed. We anticipate that this article will guide biologists and chemists in efficiently and accurately identifying cryptic pockets present in “undruggable” targets to facilitate relevant drug discovery.

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.