Latest ArticlesGut microbiome and their metabolites are closely related to human diseases, which influence the development of diseases by interacting with receptors. G protein-coupled receptor (GPCR) is a receptor superfamily that exists on the surface of cell membrane, which is involved in a wide range of human physiological activities. GPCR is currently considered as important drug targets. Traditional Chinese medicines (TCM) are characterized by multi-components, multi-targets, and multi-pathways. More and more studies have demonstrated that TCM can ultimately intervene in diseases by modulating gut microbiome and their metabolites, affecting their interactions with GPCR. This review discusses the status of gut microbiome and human diseases, the interactions of gut microbiome and their metabolites with GPCR, and the status of GPCR drug development. Based on the above contents, a new model of "TCM-gut microbiome panel-GPCR-disease" is proposed. The interactions between active ingredients of TCM, gut microbiome panel, and GPCR and their effects on disease are elucidated through multi-omics techniques. This review will provide new ideas for analyzing the pharmacological mechanism of TCM efficacy and searching for new targets of TCM.
Eleven compounds were isolated from the ethyl acetate fraction of the 95% aqueous ethanol extract of the roots of Sophora tonkinensis by silica gel, ODS, Sephadex LH-20 column chromatography, and semi-preparative RP-HPLC. Their structures were identified as 7-hydroxy-8-isopentenylchromone (1), furo[2, 3-f]-1, 3-benzodioxole-7-carboxylic acid (2), 6-[3-(2′, 4′-dihydroxyphenyl)acryloyl]-7-hydroxy-2, 2-dimethyl-8-(3-methyl-2-butenyl)-2H-benzopyran (3), flemichapparin B (4), tectorigenin (5), genistein (6), 6-hydroxy-1, 3-benzodioxole-5-carboxylic acid (7), vanillic acid (8), protocatechuic acid (9), 2, 4-dihydroxybenzoic acid (10), and p-hydroxybenzoic acid (11) through extensive spectroscopic data (IR, UV, HR-ESI-MS, and NMR spectra). Among them, compounds 1 and 2 were new compounds. In addition, compound 3 showed significant α-glucosidase and protein tyrosine phosphatase-1B (PTP1B) inhibitory activities with IC50 values of 5.595 and 0.320 μmol·L-1, respectively.
Heat shock protein 90 (HSP90) is a crucial molecular chaperone responsible for the activation and maturation of client proteins. Targeting HSP90 can effectively inhibit cancer cell proliferation by either competitively occupying the ATP-binding site or disrupting the protein-protein interaction sites between HSP90 and its co-chaperones. Therefore, studying the recognition and function of HSP90 binding sites is essential for molecular discovery. This study focuses on peptide P1, revealing its dual binding mechanism with HSP90. P1 is capable of simultaneously interacting with both the ATP-binding site of HSP90 and the binding interface with the co-chaperone CDC37 (cell division cycle 37). Through ATPase and Co-IP assays, we found that P1 effectively inhibits both ATP activity and the protein interaction between HSP90 and CDC37, providing a novel approach for developing new inhibitors targeting the HSP90 chaperone system.
Folding and post-translational modification of proteins are vital for their proper functionality, with various functional regulatory systems playing significant roles, including molecular chaperone systems, ubiquitination systems, phosphorylation systems, acetylation systems, etc. Precise regulations of these systems have emerged as an important trend in drug development. This review systematically summarizes the molecular control strategies related to protein folding and post-translational modification, with a specific focus on the molecular chaperone system and the strategy of heterobifunctional molecules. On one hand, based on the similarities and differences in molecular mechanisms and design strategies, we summarize the drug development process targeting the molecular chaperone system. On the other hand, we discuss the design principles and characteristics of dual-functional molecules, and summarize their applications and developments in the precise control of post-translational modifications, aiming to provide new insights for future design.
The anti-apoptotic members of Bcl-2 family proteins, Bcl-2 and Mcl-1, are considered therapeutic targets of various cancers. In this article, we developed four hydrophobic tag (HyT)-based protein degraders of Bcl-2/Mcl-1, based on a Bcl-2/Mcl-1 dual inhibitor S1-6, and tested their capability in Bcl-2/Mcl-1 degradation and apoptotic induction in MCF-7 cells. Interestingly, different linkers in the HyT degraders led to selective Bcl-2/Mcl-1 degradation, though the degraders S1-D1-S1-D4 maintained the pan-Bcl-2 family binding capacity. Among them, S1-D2 and S1-D4, two compounds bearing a hydrophobic linker or a PEG linker, were observed to potently and selectively induce the ubiquitination and proteasomal degradation of Bcl-2 and Mcl-1 in living cells, with a degradation rate of more than 80% or 60%, respectively. Moreover, the HyT-based degraders showed increased lethality of cancer cells compared to the parent inhibitor S1-6, demonstrating that the advantage of degraders to the occupancy-based inhibitors.
Janus kinase (JAK) and histone deacetylase (HDAC) referred to as crucial targets in autoimmune diseases and cancers have achieved quite success in the treatment of these diseases. Until now, several JAK and HDAC inhibitors have been approved. Recently, developing single multi-targeting inhibitors including JAK/HDAC dual inhibitors based on network pharmacology has made significant progress in improving therapeutic efficacy, reducing toxic and side effects, and overcoming drug resistance. In this review, we summarize novel JAK/HDAC dual inhibitors as well as JAK/HDAC-based triple-targeting inhibitors, in order to provide reference for the discovery of novel JAK/HDAC dual inhibitor.
The gut microbiota plays a crucial role in the development of colorectal cancer (CRC). The imbalanced gut microbiota causes damage to the body and disrupts bile acids metabolism, increases susceptibility to CRC, and affects the signaling of farnesol X receptor (FXR), thereby promoting CRC progression. Traditional Chinese medicine has unique advantages in the treatment of CRC due to its synergistic regulatory effects of multiple components, targets, and pathways. It can regulate gut microbiota, intervene in bile acids metabolism, and activate its receptor FXR to inhibit the occurrence and development of CRC. Based on this, this article discusses the main role of the gut microbiota-bile acids-FXR axis in the development of CRC, and reviews the anti CRC effects and mechanisms of traditional Chinese medicine intervention on gut microbiota-bile acids-FXR axis, in order to provide new ideas and methods for the prevention and treatment of CRC.
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates gene expression in a range of cells, including immune and epithelial cells. AhR signaling plays important roles in the immune system in both health and disease states. Tapinarof is a first-in-class small-molecule topical therapeutic AhR modulating agent launched for the treatment of psoriasis. To improve the activity and chemical stability of Tapinarof, a series of 2-phenylchromen-4-one derivatives were designed, synthesized and evaluated as novel AhR agonists. Compounds 5a, 5c, 5e and 5f potently activated AhR with an EC50 value of 7, 9, 6 and 6 nmol·L-1, respectively, which are 10-14 fold more potent than Tapinarof. Compounds 5a and 5e exhibit comparable inhibitory effects on IFN-γ production as Tapinarof. Furthermore, compounds 5a-5f exhibited favorable photochemical stability compared to Tapinarof. The compounds may eventually serve as lead compounds for the development of new AhR agonists.
The deubiquitinases (DUBs), as the crucial peptidohydrolases in the ubiquitin system, can reverse and strictly regulate ubiquitination and play key roles in various biological processes, including the regulation of protein stability, cell signal transduction. Ubiquitin-specific protease 28 (USP28) involves multiple cancer-related signaling pathways by enhancing the stability of various cancer-related proteins, and is closely associated with the progression of colorectal, breast cancer, lung carcinomas, and pancreatic cancer. USP28 has been considered as a promising drug target in anticancer therapy, and the development of USP28 inhibitors has made some progress. In this article, we review the structure of USP28 and its interaction with substrates, discuss the research progress of USP28 in cancers and summarize the development of USP28 inhibitors.
Twelve abietane diterpenes were isolated from the 95% ethanol fraction solvated from the aqueous extract of Styrax by using various chromatographic methods, including MCI Gel CHP 20P, Sephadex LH-20, ODS, silica gel, TLC and semi-preparative HPLC. The structures of the isolated compounds were identified by spectroscopy methods (1D, 2D NMR, UV, MS, etc.), and the absolute configuration of the new compound was determined by ECD calculations. Compound 1 is a new compound, which was identified as (4R, 5R, 9S, 10R, 12S)-12-methoxy-neoabietic acid, and compounds 2-12 were isolated from Styrax for the first time.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62199257
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
