Editorial Material
Cell & Tissue Engineering
Sanne Schouten, Nick Bovee, Zicong Liu, Hendrik Marks
Summary: Epigenetic enzymes play a critical role in gene regulation during lineage commitment. In this study, Zhu et al. (2022) reveal extensive redundancy between subunits of the epigenetic regulatory Polycomb Repressive Complex 1 using a systematic knockout strategy in mouse embryonic stem cells.
Article
Oncology
Yize Li, Yongmei Zhao, Hongyan Peng, Jing Zhang, Lun Bo, Lei Wen, Wenchao Liu, Wendong Bai, Hongmei Zhang
Summary: Inhibitors of histone deacetylases (HDACi) have shown promising effects in preclinical applications for the treatment of many diseases. However, the effects of the HDACi trichostatin A (TSA) on angiogenesis vary among different diseases. This study investigated the direct effects of TSA on endothelial cells and identified novel mechanisms underlying its effects on angiogenesis.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Matthew J. Kling, Varun Kesherwani, Nitish K. Mishra, Gracey Alexander, Erin M. McIntyre, Sutapa Ray, Kishore B. Challagundla, Shantaram S. Joshi, Don W. Coulter, Nagendra K. Chaturvedi
Summary: This study suggests that dual-inhibition of BET and HDAC proteins may be a novel therapeutic approach for MYC-driven MB.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Infectious Diseases
Thomas Mouveaux, Dante Rotili, Tom Boissavy, Emmanuel Roger, Christine Pierrot, Antonello Mai, Mathieu Gissot
Summary: This study identified a potent HDAC inhibitor compound, MC1742, which showed activity in inhibiting the growth of Toxoplasma gondii in vitro and preventing the consequences of the acute disease in vivo. The compound induced hyper-acetylation of histones and changed the parasite's gene expression program, leading to parasite death.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Chemistry, Medicinal
Chen Chen, Hongrui Chu, Anyang Wang, Huanhuan Yin, Yanqiao Gao, Shuhua Liu, Wei Li, Leiqiang Han
Summary: Incorporating a DNA-binding fragment in HDAC inhibitors has been proven effective in treating hematologic malignancies. However, these inhibitors have poor effects on solid tumors. In this study, a series of 2,5-diphenyl-1,3,4-thiadiazole hydroxamate derivatives were designed and synthesized as HDAC inhibitors with DNA binding affinity. Among them, compound 4j showed the strongest inhibitory activity against HDAC1 and demonstrated potent antiproliferative activity in tumor cell lines. Additionally, compound 4j enhanced the acetylation of histone H3 and alpha-tubulin, as well as activated caspase 3 in HCT116 and MC38 cell lines, leading to significant suppression of tumor growth in the MC38 tumor model. This work validates compound 4j as a promising lead compound for further optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Qinghua Ren, Wenqian Gao
Summary: Developing dual BET/HDAC inhibitors may provide a more effective option for cancer treatment. Designing dual inhibitors can enhance the efficacy of single-target drugs. Understanding structure-activity relationships and biological functions can facilitate rational drug design.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Qinghua Ren, Wenqian Gao
Summary: Developing dual BET/HDAC inhibitors is a rational strategy to enhance the efficacy of tumor treatment, as BET and HDAC inhibitors exhibit synergistic effects in cancer cells. This review outlines the development of dual BET/HDAC inhibitors, emphasizing their structure-activity relationships (SARs), binding modes, and biological functions.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Natalia Milosevich, Chelsea R. Wilson, Tyler M. Brown, Aktan Alpsoy, Sijie Wang, Katelyn E. Connelly, Kirsten A. D. Sinclair, Felino R. Ponio, Rebecca Hof, Emily C. Dykhuizen, Fraser Hof
Summary: Methyllysine reader proteins can alter gene transcription by binding to methylated lysine residues, impacting chromatin state or recruiting other complexes. Novel inhibitors of CBX6 and CBX8 have been discovered, showing promising effects on cell proliferation in a rhabdoid tumor cell line. This suggests the potential therapeutic value of these dual-selective inhibitors in disease treatment.
Article
Chemistry, Medicinal
Zhencheng Lai, Hao Ni, Xueping Hu, Sunliang Cui
Summary: In this study, a novel series of compounds with HDAC inhibitory activity were developed using a scaffold-hopping design. Compound 12k showed promising potential in treating hepatocellular carcinoma (HCC) and exhibited significant therapeutic efficacy in HCC cell lines and xenograft models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Mahdieh Mehrpouri, Atieh Pourbagheri-Sigaroodi, Davood Bashash
Summary: This article outlines the role of epigenetic modulations, particularly histone deacetylases, in hematologic malignancies and their therapeutic potential. Research suggests that HDACs play a significant role in hematopoiesis and the development of blood cancers.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaochen Liu, Fei Tian, Jianfeng Cui, Li Gong, Lu Xiang, Bowen Fan, Shuangteng Liu, Jiafeng Zhan, Yadi Zhou, Baichun Jiang, Molin Wang, Gongping Sun, Yaoqin Gong, Yongxin Zou
Summary: Lung cancer is the leading cause of cancer-related death worldwide, and KRAS mutations are the most common oncogenic alterations found in lung cancer. This study reveals the tumor-suppressive functions of CUL4B protein in KRAS-mutant lung cancer, as its knockout or knockdown promotes the growth and progression of lung adenocarcinoma. The study also elucidates the role of CUL4B in regulating CXCL2 and MDSCs migration to inhibit tumor development.
Article
Immunology
Nisha Holay, Alexander Somma, Mark Duchow, Milad Soleimani, Anna Capasso, Srividya Kottapalli, Joshua Rios, Uma Giri, Jennifer Diamond, Anna Schreiber, Anthony D. Piscopio, Carla van den Berg, S. Gail Eckhardt, Todd A. Triplett
Summary: Histone deacetylase inhibitors (HDACi) have potential for the treatment of malignancies, but their direct effects on T cells need further investigation. This study found that a novel class-selective HDACi rapidly increased CD4 and CD8 T cell frequencies in the blood, but the effects were transient. Therefore, treatment regimens combining HDACi with immunotherapy should take into account acute T cell effects.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Pasquale Linciano, Rosaria Benedetti, Luca Pinzi, Fabiana Russo, Ugo Chianese, Claudia Sorbi, Lucia Altucci, Giulio Rastelli, Livio Brasili, Silvia Franchini
Summary: HDAC inhibitors play a significant role in cancer treatment, but their lack of selectivity is a major drawback. Researchers have explored novel linker chemotypes to achieve selective inhibition of different HDAC isoforms. Through in vitro tests and docking calculations, it was found that some candidates could selectively inhibit HDAC1 or HDAC6.
BIOORGANIC CHEMISTRY
(2021)
Article
Oncology
Wiktoria Blaszczak, Geng Liu, Hong Zhu, Wojciech Barczak, Amit Shrestha, Gulsah Albayrak, Shunsheng Zheng, David Kerr, Anastasia Samsonova, Nicholas B. La Thangue
Summary: Aberrant protein acetylation is strongly associated with tumorigenesis, and targeting histone deacetylase (HDAC) through small-molecule inhibitors has been a focus in clinical trials. The novel HDAC inhibitor CXD101 has shown effects on gene expression in human and murine colorectal cancer cells, particularly related to immune-relevant concepts. By reinstating immune-relevant gene expression in the tumor microenvironment and enhancing antitumor activity when combined with immune checkpoint inhibitors, CXD101 presents a powerful rationale for exploring combination therapy in human cancers.
MOLECULAR ONCOLOGY
(2021)
Review
Chemistry, Medicinal
Daniel Alencar Rodrigues, Andrew Roe, Darren Griffith, Triona Ni Chonghaile
Summary: Thanks to modern chemistry, previously undruggable substrates can now be targeted using the ubiquitin-proteasomal degradation system. PROteolysis TArgeting Chimeras (PROTACs) are heterobifunctional molecules designed to degrade target proteins, and they have garnered significant interest in industry and academia. Recent advances in PROTAC-mediated degradation of histone deacetylases (HDACs) offer advantages over direct inhibition, making them potential therapeutic agents for various disease pathologies.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
