Review
Immunology
Ya-Tao Wang, Wei-Dong Ji, Hong-Mei Jiao, Ang Lu, Kun-Feng Chen, Qi-Bing Liu
Summary: This review provides an overview of the potential of 4-1BB as an immunotherapeutic target, discussing its role in the tumor microenvironment and tumor progression, as well as the latest developments in drug targeting 4-1BB.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Shin-Yi Chung, Yu-Chan Chang, Dennis Shin-Shian Hsu, Ya-Chi Hung, Meng-Lun Lu, Yi-Ping Hung, Nai-Jung Chiang, Chun-Nan Yeh, Michael Hsiao, John Soong, Yeu Su, Ming-Huang Chen
Summary: CX-5461 can enhance the efficacy of immune checkpoint inhibitors in the treatment of colorectal cancer by altering the tumor microenvironment and activating the interferon signaling pathway. In addition, CX-5461 can inhibit tumor growth by increasing PD-L1 expression and cytotoxic T-cell numbers.
Review
Biochemistry & Molecular Biology
Fernand Bteich, Mahshid Mohammadi, Terence Li, Muzaffer Ahmed Bhat, Amalia Sofianidi, Ning Wei, Chaoyuan Kuang
Summary: Colorectal cancer is a heterogeneous disease with various alterations at the cellular and molecular levels. KRAS mutations are found in up to 40% of CRCs and serve as both a prognostic and predictive biomarker. Targeting KRAS mutations in CRC is being explored through both indirect and direct strategies, with several KRAS allele-specific inhibitors in late-phase clinical trials and newer agents and targeting strategies undergoing preclinical and early-phase clinical testing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
Xiaojuan Jia, Xin Han
Summary: Inhibition of androgen receptor (AR) has been extensively studied for treating prostate cancer, but resistance mechanisms limit its efficacy. Small-molecule PROTAC AR degraders have emerged as a new therapeutic strategy to overcome resistance mechanisms. In the last two decades, potent PROTAC AR degraders have shown promising results in preclinical and clinical trials, with ARV-110 demonstrating good clinical effects in patients with mCRPC. This highlights the high clinical value of PROTAC strategy in treating human diseases. This review summarizes the recent advances in the development of potential clinical-stage PROTAC AR degraders.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Chemistry, Medicinal
Sapana Bansod, Mohd Aslam Saifi, Chandraiah Godugu
Summary: This review highlights the pharmacological activities and mechanisms of berberine in liver diseases, as well as the pharmacokinetic and toxicological barriers of this promising phytoconstituent. Berberine has demonstrated hepatoprotective effects by modulating multiple signaling pathways implicated in the pathogenesis of liver diseases.
PHYTOTHERAPY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Kangkang Niu, Xiaojuan Zhang, Qisheng Song, Qili Feng
Summary: This study demonstrates that RBM4 promotes mRNA translation of the VEGFA gene by binding to the G4 structure in the IRES.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Ping Ling, Xueying Zheng, Sihui Luo, Junbo Ge, Suowen Xu, Jianping Weng
Summary: ASCVD is the largest cause of morbidity and mortality worldwide, with lipid-lowering therapies as the current major cornerstone of its management. However, some patients do not respond to standard therapies and remain at high risk of ASCVD.
DIABETES OBESITY & METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Swati Chaudhary, Mohan Kumar, Mahima Kaushik
Summary: G-quadruplexes play significant roles in various diseases and have been extensively studied. Further understanding of these structures and their stabilizing or destabilizing ligands can facilitate future drug discovery.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Medicinal
Chiara Platella, Ettore Napolitano, Claudia Riccardi, Domenica Musumeci, Daniela Montesarchio
Summary: Naphthalene diimides (NDIs) show high potential as anticancer agents by targeting multiple G-quadruplexes simultaneously and demonstrating strong, selective anticancer activity. Analysis of biophysical and biological data yields structure-activity correlations, while in-depth discussion of NDI binding modes to G-quadruplexes is based on available structural models.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Emanuela Ruggiero, Irene Zanin, Marianna Terreri, Sara N. Richter
Summary: G-quadruplexes (G4s) play a crucial role in regulating key cellular processes, especially in cancer and virology. The use of selective G4 ligands helps understand the complexity of G4-mediated mechanisms in the viral life cycle, presenting a promising emerging antiviral approach.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Joana Figueiredo, Andre Miranda, Jessica Lopes-Nunes, Josue Carvalho, Daniela Alexandre, Salete Valente, Jean-Louis Mergny, Carla Cruz
Summary: This study investigated the formation of an RNA quadruplex structure in the human precursor pre-MIR150 sequence with the potential to recognize NCL. The results showed that rG4 has high thermal stability and similar binding affinities to PhenDC3 and NCL RBD1,2, indicating its potential as a detection probe for LC in liquid biopsies. The labeled rG4 could be used for its non-invasive detection in LC patients.
BIOCHEMICAL PHARMACOLOGY
(2021)
Editorial Material
Oncology
Paul C. McDonald, Shawn C. Chafe, Claudiu T. Supuran, Shoukat Dedhar
Summary: Tumor hypoxia is a significant problem in cancer treatment, as hypoxic tumor cells are resistant to most therapies and display aggressive behavior. Carbonic Anhydrase IX (CAIX) has attracted attention as a therapeutic target because of its selective expression on hypoxic tumor cells. This article discusses the current status and future strategies for targeting CAIX in cancer therapy.
Review
Chemistry, Medicinal
Francesca Romano, Anna Di Porzio, Nunzia Iaccarino, Gelsomina Riccardi, Ritamaria Di Lorenzo, Sonia Laneri, Bruno Pagano, Jussara Amato, Antonio Randazzo
Summary: Modulation of G-quadruplex (G4) formation has been proposed as a powerful tool for cancer treatment through the control of oncogene expression. This review provides an overview of current knowledge on G4s in human oncogene promoters and the most representative G4-binding ligands. Targeting G4s has the potential to develop novel and highly specific anticancer drugs capable of selectively impacting gene expression.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Chemistry, Multidisciplinary
Chuanqi Zhao, Geng Qin, Jingsheng Niu, Zhao Wang, Chunyu Wang, Jinsong Ren, Xiaogang Qu
Summary: Researchers found that specific sequences in the SARS-CoV-2 genome can form G4 structures, and their biofunctions can be regulated by specific compounds, providing new insights for developing novel antiviral drugs against COVID-19.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Cell & Tissue Engineering
Maria Rosaria Ambrosio, Teresa Migliaccio, Fabiana Napolitano, Sarah Di Somma, Giovanni Maneli, Jussara Amato, Bruno Pagano, Antonio Randazzo, Giuseppe Portella, Pietro Formisano, Anna Maria Malfitano
Summary: In this study, the role of G4 motifs in adipogenic differentiation was investigated using human adipose-derived mesenchymal stem cells (ASCs). The results showed that G4 structures were increased in differentiated adipocytes compared to their precursors, and treatment with the G4 ligand Braco-19 reduced G4 content in the mature adipocytes. Furthermore, Braco-19 caused morphological changes and reduced lipid droplet formation and key gene expression in the mature adipocytes. These findings reveal a new role of G4 motifs in human adipocyte differentiation.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)