Article
Cell Biology
Yuqi Guo, Fangxi Xu, Scott C. Thomas, Yanli Zhang, Bidisha Paul, Satish Sakilam, Sungpil Chae, Patty Li, Caleb Almeter, Angela R. Kamer, Paramjit Arora, Dana T. Graves, Deepak Saxena, Xin Li
Summary: Periodontal disease is a common inflammatory disease caused by oral microbial dysbiosis, leading to inflammation and bone loss. This study shows that succinate, which is elevated in the subgingival plaque of patients with severe periodontal disease, activates SUCNR1 and contributes to the development of periodontitis. Therapeutic studies demonstrate that a SUCNR1 antagonist can inhibit inflammation and reduce periodontal bone loss.
Article
Cell Biology
Namin Duan, Xiaohui Hu, Huiran Qiu, Rui Zhou, Yuru Li, Wenxia Lu, Yamin Zhu, Shuang Shen, Wenhui Wu, Feifei Yang, Ning Liu
Summary: In this study, a novel and efficient HDAC1 inhibitor called HR488B was found to exhibit effective anti-colorectal cancer (CRC) activity. HR488B induced cell cycle arrest and apoptosis in CRC cells by causing mitochondrial dysfunction, reactive oxygen species (ROS) generation, and DNA damage accumulation. Furthermore, HR488B suppressed the growth of CRC cells by decreasing the expression of E2F1 and preventing its release from the E2F1/Rb/HDAC1 complex. Therefore, HR488B may be a potential candidate for CRC therapy and targeting the E2F1/Rb/HDAC1 axis shows promise as a therapeutic approach for CRC.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Yajing Xing, Weikai Guo, Min Wu, Jiuqing Xie, Dongxia Huang, Pan Hu, Miaoran Zhou, Lin Zhang, Qiansen Zhang, Peili Wang, Xin Wang, Guixue Wang, Huangan Wu, Cili Zhou, Yihua Chen, Mingyao Liu, Zhengfang Yi, Zhenliang Sun
Summary: Researchers have identified a small molecule compound named WK500B that can block the inhibition of BCL6, reactivate target genes, kill DLBCL cells, and display strong anti-tumor effects in animal models. Therefore, WK500B holds promise as an effective orally available therapeutic agent for DLBCL.
Article
Oncology
Yinan Wang, Chuanhe Yang, Michelle M. Sims, Joshua R. Sacher, Mithun Raje, Hemantkumar Deokar, Peibin Yue, James Turkson, John K. Buolamwini, Lawrence M. Pfeffer
Summary: In this study, a novel small molecule SS-4 was designed to specifically interact with STAT3 and showed strong inhibition of Y705 phosphorylation. SS-4 induced apoptosis and inhibited proliferation in GBM cells in a Y705 phosphorylation-dependent manner. It also had anti-tumor effects in vivo, suggesting its potential as a therapeutic agent for GBM.
Article
Medicine, Research & Experimental
Guang Xu, Shubin Fu, Xiaoyan Zhan, Zhilei Wang, Ping Zhang, Wei Shi, Nan Qin, Yuanyuan Chen, Chunyu Wang, Ming Niu, Yuming Guo, Jiabo Wang, Zhaofang Bai, Xiaohe Xiao
Summary: This study identified echinatin, a component of traditional herbal medicine licorice, as a potentially novel inhibitor of NLRP3 inflammasome activation in both in vitro and in vivo models. Echinatin was shown to exert inhibitory effects through its interaction with heat-shock protein 90 (HSP90), disrupting the formation of the HSP90-NLRP3 complex. The administration of echinatin demonstrated significant suppression of NLRP3 inflammasome activation and amelioration of inflammatory conditions in mouse models, suggesting its potential as a therapeutic approach for NLRP3-driven diseases.
Review
Oncology
Haolan Wang, Ming Guo, Hudie Wei, Yongheng Chen
Summary: MCL-1, an antiapoptotic protein, is frequently overexpressed in many tumor types and closely associated with tumorigenesis, poor prognosis, and drug resistance. Its central role in regulating the mitochondrial apoptotic pathway makes it an attractive target for cancer therapy. Progress has been made towards MCL-1 inhibitors and some have entered clinical trials.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Chemistry, Medicinal
Lixin Zhou, Tianyu Wang, Kuojun Zhang, Xiangyu Zhang, Sheng Jiang
Summary: Hematopoietic progenitor kinase 1 (HPK1) is a serine/threonine protein kinase that negatively regulates T cells, B cells, and dendritic cells-mediated immune responses. It plays a role in cellular processes such as immune cell activation, differentiation, proliferation, adhesion, and apoptosis. HPK1 is associated with the occurrence and development of human malignant tumors, making it a promising target for cancer immunotherapies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Julie Devin, Tatiana Caneque, Yea-Lih Lin, Lucie Mondoulet, Jean-Luc Veyrune, Matthieu Abouladze, Elvira Garcia De Paco, Ouissem Karmous Gadacha, Guillaume Cartron, Philippe Pasero, Caroline Bret, Raphael Rodriguez, Jerome Moreaux
Summary: Diffuse large B-cell lymphoma (DLBCL) is a common hematological malignancy, and alterations in iron metabolism may be targeted for therapy. Iron score (IS), a gene expression-based risk score, can identify high-risk DLBCL patients who may benefit from targeting iron homeostasis. Ironomycin, a potential treatment for DLBCL, inhibits cell proliferation and induces cell death.
Article
Cell Biology
Daming Zuo, Yu Chen, Jian-piao Cai, Hao-Yang Yuan, Jun-Qi Wu, Yue Yin, Jing-Wen Xie, Jing-Min Lin, Jia Luo, Yang Feng, Long-Jiao Ge, Jia Zhou, Ronald J. Quinn, San-Jun Zhao, Xing Tong, Dong-Yan Jin, Shuofeng Yuan, Shao-Xing Dai, Min Xu
Summary: The twenty-first century has witnessed more than ten major epidemics or pandemics, including the devastating COVID-19. There is an urgent need for novel antiviral drugs with broad-spectrum coverage. This study reports a new broad-spectrum antiviral compound called PAC5. Oral administration of PAC5 was found to eliminate HBV cccDNA and reduce antigen load in mouse models of HBV infection. Additionally, PAC5 significantly decreased viral loads and attenuated lung inflammation in a hamster model of SARS-CoV-2 omicron (BA.1) infection. The mechanism behind these effects involves activation of hnRNPA2B1 and the TBK1-IRF3 pathway, leading to the production of antiviral type I IFNs. These findings suggest that PAC5 could be a promising option for dealing with emerging infectious diseases.
Review
Biochemistry & Molecular Biology
Marianna Nalli, Domiziana Masci, Andrea Urbani, Giuseppe La Regina, Romano Silvestri
Summary: This review discusses the recent advances in small molecule beta-catenin agents, including the structure-activity relationships and biological activities of inhibitors, providing useful knowledge for the discovery of therapeutic beta-catenin drugs for cancer treatment.
Article
Biochemistry & Molecular Biology
Jie Yang, Weibin Gong, Si Wu, Hong Zhang, Sarah Perrett
Summary: Hsp70 proteins are ancient chaperones with important roles in cellular processes, making them potential drug targets for diseases like cancer. The inhibitor PES has been shown to interact with specific residues in Hsp70, affecting its structure and function similarly to glutathionylation. This study provides insights into developing covalent inhibitors for Hsp70.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Reka Rahel Bicsko, Lili Antal, Ferenc Magyari, Robert Szasz, Miklos Udvardy, Arpad Illes, Lajos Gergely
Summary: Treating relapsed and refractory diffuse large B-cell lymphoma remains challenging. CAR-T cell therapy has changed the role of autologous stem cell transplantation in these patients. The aim of this retrospective study was to evaluate the results of autologous transplantation and identify factors affecting the outcomes. Among 116 DLBCL patients, the median event-free survival and overall survival were 75 months and 105 months, respectively. Prognostic markers at diagnosis had no impact on the transplantation outcome. Consolidative autologous transplantation is an effective treatment option for eligible patients with DLBCL and can benefit those not achieving complete response before transplantation.
Article
Microbiology
Jiao Zhang, Li Shen, Peiyao Zhou, Shuying Chen, Bingjie Wang, Cailin Wan, Weihua Han, Lulin Rao, Huilin Zhao, Xinyi Wang, Chunyang Wu, Junhong Shi, Yanghua Xiao, Zengqiang Song, Fangyou Yu, Chunchan Lin
Summary: This study demonstrates that a small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus. It reduces biofilm mass and suppresses the production of polysaccharide intercellular adhesin, thus preventing cell adhesion. Importantly, S-342-3 shows excellent biosafety without toxic effects on cells and animals.
MICROBIOLOGY SPECTRUM
(2023)
Review
Biochemistry & Molecular Biology
Andrew R. Conery, Jennifer L. Rocnik, Patrick Trojer
Summary: The approval of the first histone methyltransferase inhibitor in 2020 marks a significant milestone in the field of targeted manipulation of chromatin regulatory pathways for cancer treatment. Despite the complexity of identifying key targets for therapeutic intervention, approaches in chemical biology have played a critical role in discovering key nodes in these pathways and translating them into potential cancer therapies. This review highlights the importance of chemical probes, drug candidates, and translational strategies in maximizing the impact of epigenetic writer enzymes in cancer therapy.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Viktoria K. Ilic, Olga Egorova, Ernest Tsang, Milena Gatto, Yi Wen, Yong Zhao, Yi Sheng
Summary: The proto-oncogene MDM2 is frequently amplified in many human cancers and its overexpression is associated with poor prognosis. MDM2 shows oncogenic activity by negatively regulating tumor suppressor p53 and proteins involved in DNA repair, cell cycle control, and apoptosis pathways. Inhibition of MDM2 activity has been pursued as an attractive direction for anti-cancer therapeutics. This study identified a biflavonoid compound Hinokiflavone as a promising candidate compound targeting MDM2. Hinokiflavone was shown to bind the MDM2-MDMX RING domain and inhibit MDM2-mediated ubiquitination in vitro. Hinokiflavone treatment downregulated MDM2 and MDMX and induced apoptosis in various cancer cell lines. Hinokiflavone demonstrated tumor-suppressive activity that is both p53-dependent and -independent.
