Latest ArticlesL-Asparaginase (ASNase), an aminohydrolase, is widely utilized in the pharmaceutical and food industries. Among its various sources, Escherichia coli K12-derived EcASNase has been employed as a clinical drug for the treatment of acute lymphoblastic leukemia (ALL). However, the limited catalytic activity and stability of EcASNase have restricted its broader application in medicine and food processing. In this study, a random mutagenesis library was constructed via error-prone PCR, followed by high-throughput screening using a coupled bacterial growth strategy. Three positive mutants with enhanced activity were identified: G38S, Q212Y, and S274P, exhibiting activities 1.4-, 1.1-, and 1.2-fold higher than the wild type (WT), respectively. Saturation mutagenesis libraries were subsequently generated for positions 38, 212, and 274, leading to the identification of mutants G38A, G38S, G38Q and G38V, with kcat/Km values 1.7-, 1.5-, 2.1-, and 2.2-fold higher than WT, respectively. Among these, G38V emerged as the most active mutant, with a Tm value increased by 8.4 ℃ compared to WT. Combination mutations, such as G38V/Q212F and G38V/S274P, failed to yield further activity improvements. This research elucidates the contributions of critical residues to the enzyme's activity and stability, providing novel insights into the rational design and development of therapeutic enzymes.
In 2024, drug discovery continues to develop on the basis of the achievement before. The number of approved first-in-class (FIC) drugs reach a higher level. The Center for Drug Evaluation and Research of U.S. Food and Drug Administration has totally approved 50 novel drugs, including 30 small molecule drugs and 20 macromolecule drugs. Comparing to the number of approved drugs in 2023, the total in 2024 falls slightly. But the proportion of FIC drugs increase obviously. There are 24 FIC drugs (48%) approved in 2024, which include 13 FIC small molecule drugs and 11 FIC macromolecule drugs and whose indications mainly focus on tumor, and endocrine and metabolic disease. Among 24 FIC drugs, many drugs have breakthrough clinical value, such as the first combination of muscarinic acetylcholine receptor M1/M4 agonist and peripheral muscarinic acetylcholine receptor antagonist, xanomeline and trospium chloride, the first thyroid hormone receptor beta agonist, resmetirom, the first dual antagonist of endothelin receptor type A and B to treat hypertension, aprocitentan. The huge value of FIC drugs in clinical therapy, academic research and commerce, is attracting wide attention from the patients, researchers and enterprises. This review will analyze the research background, development process and therapeutic application of three first-in-class small molecule drugs in this year from a medicinal chemistry perspective, expecting to provide more research directions and methods for the development and research of FIC drugs.
Exosomes are small vesicles secreted by cells that contain important bioactive molecules such as nucleic acids and proteins. Increasing research indicates that exosomes play a unique and crucial role as signal molecule carriers in various diseases, and they exhibit great potential in disease diagnosis and treatment. Recent studies have shown that exosomes play an important role in immune regulation. The NOD (nucleotide binding oligomerization domain)-like receptors protein 3 (NLRP3), an essential component of the innate immune system, plays a key role in the occurrence and development of various diseases including autoimmune diseases, metabolic diseases, and neurodegenerative diseases. Its activation and regulatory mechanisms are complex and diverse. However, the regulatory mechanisms associated with exosomes and NLRP3 inflammasome have not yet been fully elucidated. This article reviews the regulatory effects of exosomes from different sources on the NLRP3 inflammasome and summarizes the therapeutic potential of exosomes in diseases associated with the NLRP3 inflammasome, aiming to provide new ideas for the prevention and treatment of diseases related to the NLRP3 inflammasome.
Radiopharmaceuticals play a crucial role in nuclear medicine, with the development of radioligands being a key focus in this field. Peptide-based radiopharmaceuticals have shown significant advantages in clinical applications, with the majority of FDA-approved targeting radiopharmaceuticals since 2018 being derived from peptides or peptidomimetics. Bicyclic peptides have emerged as a promising targeting moiety in radioligands, offering improved biophysical properties compared to linear or monocyclic peptide ligands. This article provides an overview of the methods for obtaining bicyclic peptide ligands, as well as highlighting the major clinical and preclinical advancements in bicyclic peptide-based radiopharmaceuticals. The review also discusses the future prospects of bicyclic peptide-based radiopharmaceuticals, offering insights for practitioners in the field of pharmaceutical science and nuclear medicine to keep up with the latest developments in radiopharmaceutical innovation.
Respiratory infections, as common diseases, along with other respiratory system diseases such as asthma, rare diseases including cystic fibrosis, chronic obstructive pulmonary disease, and lung cancer, can be prevented using vaccines. Taking respiratory infections as an example, vaccines are mostly administered via intramuscular injection, inducing the production of serum IgG, thereby neutralizing viral infectivity and alleviating COVID-19 symptoms. However, due to the lack of secretory IgA and IgG in muscle tissues, intramuscular vaccines cannot quickly provide protection to the respiratory tract. To overcome the shortcomings of intramuscular injection, some vaccine candidates for nasal or nebulized inhalation are under development or have been approved. Clinical studies show that inhaled vaccines can induce antibody responses similar to those of intramuscular vaccines at much lower doses. Inhaled vaccines can simultaneously induce humoral, cellular, and mucosal immunity, providing triple protection. With the application of new vaccines (e.g. mRNA vaccines and DNA vaccines) in inhalable formulations for COVID-19, inhaled vaccines have been proven to have broad application prospects in the prevention of lung diseases. Given this background and the known abundance of immune cells in the lungs, increasing research efforts are devoted to developing single-dose inhalable nano dry powder vaccines. This article discusses the roles and advantages of inhaled vaccines in mucosal immunity, their potentials for treating different diseases, and prospects for the future development of inhaled vaccines based on nanotechnology.
Human influenza is mainly caused by influenza A virus and influenza B virus, and it is one of the most serious infectious diseases that pose a serious threat to human health. Currently, there are few marketed drugs for influenza viruses, and the existing drugs are faced with problems such as drug resistance. The development and research of combinations of anti-influenza drugs have gradually attracted people's attention. At present, certain progress has been made in aspects such as the discovery of anti-influenza drug combinations and the evaluation of drug effects. Discovering effective combination drugs is an ideal method for repurposing old drugs. That can be used to improve therapeutic effects and delay or reduce the occurrence of drug resistance. Herein, this article introduces the evaluation methods, models of combinations of anti-influenza drugs, as well as available data resources and tools, and summarizes the latest progress in the current research on combinations of anti-influenza drugs, with the aim of providing a reference for the research and development of the combined application of anti-influenza virus drugs.
Human cytomegalovirus (HCMV) infection poses significant morbidity and/or mortality risks for individuals with compromised immune systems, rendering it one of the most prevalent congenital infections worldwide. The pursuit of HCMV vaccines has spanned over five decades, with clinical trials primarily focusing on various vaccine candidates, including live attenuated vaccines, viral vectored vaccines, subunit vaccines, peptide vaccines, DNA vaccines, RNA vaccines, and viral-like particle vaccines, usually accompanied by the use of adjuvants. Although the development of vaccines against HCMV is being actively promoted, there are still numerous obstacles and challenges persisting in the research process, due to unique pathogenic characteristics and infection mechanisms of HCMV. Based on the summarized research progress, this article analyzes and discusses the faced challenges and potential approaches to provide valuable insights and guidance for the exploration and development of new vaccines candidates, and ultimately achieve prevention and control of HCMV infection.
Immune checkpoint inhibitors (ICIs) have emerged as critical agents in cancer immunotherapy; however, their resistance and limited response in most patients pose significant challenge. The gut microbiota, as a pivotal immune regulator, has been increasingly recognized for its role in enhancing the therapeutic efficacy of ICIs. Studies demonstrate that fecal microbiota transplantation or transplantation of specific bacterial strains can directly reshape the gut microbiota composition, thereby improving ICI therapeutic outcomes. Furthermore, dietary interventions, prebiotics, and postbiotics have shown potential in augmenting the anti-tumor effects of ICIs through gut microbiota modulation. Despite these promising findings, further investigations are required to optimize microbiota-based strategies and therapeutic protocols. This review highlights the critical role of gut microbiota modulation in ICI-based cancer therapy and explores its clinical applications, offering both practical insights and theoretical foundations for improving immunotherapy outcomes against various cancers.
There are abundant resources of traditional Chinese medicine in China, and it is found that the effective components of traditional Chinese medicine contain functional groups that are easy to coordinate with metal ions, such as amino, carboxyl and hydroxyl, which can complex with transition metal ions to derive new compounds. These traditional Chinese medicine metal complexes often exhibit unique properties and functions compared with their corresponding monomers, providing a new path for new drug development. Based on the formation principle of metal complexes with traditional Chinese medicine and the common coordination metal ions, in this review, the effective components in traditional Chinese medicine are roughly divided into anthraquinone, alkaloid, flavone, coumarin, amino acids and polysaccharide compounds, so as to provide new ideas for the discovery of new traditional Chinese medicine, and provide scientific basis for the modernization and internationalization of traditional Chinese medicine.
Gliomas are the most common primary tumors in the central nervous system. However, the efficacy of first-line treatments for glioma is hindered by the blood brain barrier (BBB), making it difficult to reach an effective dose at the tumor site. The volatile oil from traditional Chinese medicine have the advantages of high fat solubility and ability to penetrate the blood brain barrier, has demonstrated promising inhibitory effects on glioma. The volatile oil components of traditional Chinese medicine can improve the anti-glioma efficacy by promoting the entry of chemotherapeutic drugs into the brain, inhibiting the exocytosis of drugs within the brain and synergizing with chemical drug therapy. However, the stability of volatile oil is poor, nano-formulations including liposomes, nanoparticles, and self-assembled prodrug delivery systems, can improve their stability and exert the therapeutic efficacy. As an effective drug for the treatment of glioma, volatile oil from traditional Chinese medicine shows good prospects for application. This review summarizes the mechanisms of action of volatile oil from traditional Chinese medicine and their main components against glioma, and the research progress of volatile oil combined with chemotherapeutic drugs or designed as nano-drug delivery systems for glioma therapy, with a view to providing reference for the application of volatile oil from traditional Chinese medicine in the treatment of glioma.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
