Article
Chemistry, Multidisciplinary
Xiangbo Yang, Huimin Lu, Hang Xie, Binbin Zhang, Tianqing Nie, Chen Fan, Tao Yang, Yechun Xu, Haixia Su, Wei Tang, Bing Zhou
Summary: Sepsis, identified by its high risk of life-threatening organ dysfunction, is considered a major cause of health loss, with the World Health Organization labeling it as the most urgent unmet medical need in 2017. The discovery of the role of RIPK1 in sepsis has led to the development of potentially effective therapeutic strategies such as the highly potent compound ZB-R-55, which shows promising therapeutic effects in preclinical studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Xiaoyan He, Min Li, Zhi Ye, Xiaoling You, Jia Wang, Xin Xiao, Guofeng Zhu, Jun Wei, Yunhong Zha
Summary: In this study, it was found that piperlongumine, an alkaloid isolated from the long pepper plant, has inhibitory effects on excessive necroptosis, which contributes to the pathogenesis of various inflammatory and neurodegenerative diseases. The results showed that piperlongumine significantly improved cell viability and inhibited TNF alpha-induced systemic inflammatory response syndrome (SIRS) in mice. Therefore, piperlongumine has potential clinical translation value for the treatment of diseases associated with necroptosis and SIRS.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2023)
Editorial Material
Chemistry, Multidisciplinary
Xinyu Ling, Tao Liu
Summary: Wang and his team provide an elegant selection platform to identify the targets of a nonproliferative drug by linking transcription activation to a suicide gene.
ACS CENTRAL SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Md Kabir, Elias C. Padilha, Pranav Shah, Ruili Huang, Srilatha Sakamuru, Eric Gonzalez, Lin Ye, Xin Hu, Mark J. Henderson, Menghang Xia, Xin Xu
Summary: CYP3A7 is an important xenobiotic metabolizing enzyme in the liver of human embryos, fetuses, and newborns. We identified chemical features important for CYP3A7 selectivity and established a dataset for future drug metabolism and interaction studies.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Miaomiao Liu, Wesley C. Van Voorhis, Ronald J. Quinn
Summary: This article introduces a method using native mass spectrometry to explore the interaction between ligands and protein partners, successfully identifying known ligand-protein interactions in protein mixtures under different experimental conditions.
SCIENTIFIC REPORTS
(2021)
Review
Pharmacology & Pharmacy
Shang Li, Lailiang Qu, Xiaobing Wang, Lingyi Kong
Summary: This review provides a comprehensive overview of the potential role of RIPK1 in the progression of Alzheimer's disease (AD). It explores the underlying linkages between RIPK1 and AD, including neuronal death, Aβ and Tau, inflammasome activation, BBB rupture, AMPK/mTOR, mitochondrial dysfunction, and O-glcNAcylation. The review also covers the discovery of RIPK1 inhibitors, ongoing clinical trials, and future RIPK1-targeted therapeutics.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Andres Felipe Vasquez, Luis Alberto Gomez, Andres Gonzalez Barrios, Diego M. Riano-Pachon
Summary: Antifolates like methotrexate block nucleic acid synthesis and cell proliferation, but their classical structure is ineffective against melanoma. A study combining virtual screening and cell-based assays identified promising non-classical hDHFR inhibitors, with compounds C1 and C2 exhibiting activity against melanoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Peng Li, Chujie Bai, Lingmin Zhan, Haoran Zhang, Yuanyuan Zhang, Wuxia Zhang, Yingdong Wang, Jinzhong Zhao
Summary: Identifying the biological targets of a compound is crucial for understanding drug mechanisms and developing new drugs. The Connectivity Map concept connects genes, drugs, and diseases based on gene-expression signatures. However, existing methods are inefficient due to the need for reference drugs. In this study, we developed a procedure to extract target-induced gene modules and identified target gene clusters. Additionally, we proposed a gene module pair-based approach to predict novel compound-target interactions, leading to the discovery of new inhibitors for PI3K pathway proteins.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Genetics & Heredity
Zhanli Peng, Kangjie Wang, Shenming Wang, Ridong Wu, Chen Yao
Summary: This study identified TRAF5 as a diagnostic marker for necroptosis-related atherosclerosis, which can be used to diagnose and assess plaque stability in atherosclerosis.
BMC MEDICAL GENOMICS
(2023)
Review
Pharmacology & Pharmacy
Dejuan Sun, Yuanyuan Guo, Piyu Tang, Hua Li, Lixia Chen
Summary: ADP-ribosylation factor 6 (Arf6), a small G-protein, plays important roles in cellular events and cancer progression. Understanding its function and mechanism is essential for future cancer therapy. This review summarizes the structure and roles of Arf6 in cancer, and discusses its potential as a target for protein-protein interaction inhibitors.
ACTA PHARMACEUTICA SINICA B
(2023)
Review
Chemistry, Medicinal
Peng Lei, Jifa Zhang, Peiyu Liao, Changyu Ren, Jiaxing Wang, Yuxi Wang
Summary: CDK12 is a crucial kinase involved in various biological processes and associated with different types of cancer. Development of CDK12 inhibitors has faced challenges due to the similarity with CDK13, however, recent studies have made progress in this field and shed light on the structure-activity relationships for further development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yuemin Bian, Jason J. Kwon, Cong Liu, Enrico Margiotta, Mrinal Shekhar, Alexandra E. Gould
Summary: High-throughput screening methods combined with virtual screening techniques can save time and money in drug discovery. The TAME-VS platform uses machine learning models for virtual screening and efficiently identifies candidate compounds.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Chemistry, Analytical
Jim Nonomiya, Ke Sherry Li, Brett M. Babin, Melinda M. Mulvihill
Summary: Interest in covalent drug discovery has increased following the success of covalent inhibitors targeting BTK and KRAS G12C approved by the FDA. High-throughput screening by intact protein mass spectrometry is commonly used to identify lead compounds, but it does not provide binding site information. This article introduces CoMPAS, a new targeted mass spectrometry-based covalent screening method that provides binding site information in the initial screen and offers advantages such as higher sensitivity and reduced protein reagent requirements.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ravi Singh, Ankit Vyankatrao Pokle, Powsali Ghosh, Ankit Ganeshpurkar, Rayala Swetha, Sushil Kumar Singh, Ashok Kumar
Summary: LIM kinases play a crucial role in the regulation of actin dynamics. In this study, ligand-based drug design and molecular modelling were used to identify potential compounds that can inhibit LIMKs. Through comprehensive docking and molecular dynamics simulation, three virtual hits with optimal binding properties were discovered. These hits have the potential to be developed into drugs for targeting LIMKs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Biochemistry & Molecular Biology
Shivani Batra, Shagufta Jahan, Anam Ashraf, Bandar Alharby, Talha Jawaid, Asimul Islam, Imtaiyaz Hassan
Summary: Cyclin-dependent kinase 5 (CDK5) is a serine/threonine-directed kinase primarily found in the brain that plays a crucial role in the development of the central nervous system. Recent research has shown that CDK5 is activated by specific cyclins, which regulate its expression and activity. This review examines the role of CDK5 in neurons, synaptic plasticity, DNA damage repair, and the cell cycle, highlighting its therapeutic potential as a target for neurodegenerative diseases. The structural features of CDK5 and its binding with designed inhibitors are also discussed, providing insights for the development of attractive strategies in therapeutic targeting.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
