Article
Biochemistry & Molecular Biology
Anand Chopra, William G. Willmore, Kyle K. Biggar
Summary: JmjC KDMs are a type of demethylase that not only are associated with histone demethylation, but also with non-histone demethylation. Recent findings have highlighted the importance of KDM3A in promoting cancerous phenotypes, which can provide insights into the mechanisms through which it exerts its oncogenic functions.
Article
Biochemistry & Molecular Biology
Tianqi Wang, Yang Liu, Hailin Zhang, Zhen Fang, Rong Zhang, Wenqing Zhang, Yan Fan, Rong Xiang
Summary: Crystal complex structures of two KDM4D inhibitors, OWS and 10r, have been determined, offering new insights for rational design and optimization of KDM4D inhibitors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Integrative & Complementary Medicine
Li Zhong-Rui, Gu Meng-Zhen, Xu Xiao, Zhang Jing-Han, Zhang Hai-Li, Han Chao
Summary: This review highlights recent advances in natural LSD1 inhibitors, including their discovery and identification process, natural sources, chemical structures, anticancer effects, and structure-activity relationships. Natural products play an important role in drug discovery, particularly in cancer therapy.
CHINESE JOURNAL OF NATURAL MEDICINES
(2022)
Article
Cell Biology
Baoyu Chen, Yuwen Zhu, Junliang Chen, Yifei Feng, Yong Xu
Summary: This study reveals that differential TCL expression in malignant colorectal cancer cells is associated with histone H3K9 methylation, and the lysine demethylase KDM4B is essential for TCL transcription. KDM4B interacts with the transcription factor ERG1 to activate TCL transcription by facilitating the assembly of pre-initiation complex on the TCL promoter, ultimately influencing migration and invasion of CRC cells. Additionally, upregulation of KDM4B in advanced stage CRC specimens suggests it may serve as a potential therapeutic target for CRC intervention.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Fangfang Dong, Min Chen, Min Chen, Lin Jiang, Zhiming Shen, Longfei Ma, Chunsheng Han, Xudong Guo, Fei Gao
Summary: PRMT5 is abundantly expressed in spermatogonial stem cells and its deletion leads to loss of SSCs and male infertility. Deficiency of Prmt5 in SSCs results in abnormal proliferation, cell cycle arrest, and increased apoptosis, along with alterations in gene expression and histone modifications.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Melanie R. Muller, Aaron Burmeister, Margaretha A. Skowron, Alexa Stephan, Felix Bremmer, Gamal A. Wakileh, Patrick Petzsch, Karl Kohrer, Peter Albers, Daniel Nettersheim
Summary: This study identified seven drugs targeting epigenetic modifiers to treat cisplatin-resistant GCTs. Mass spectrometry-based analyses revealed effects beyond the expected mode-of-action of each drug, suggesting a wider spectrum of activity. Additionally, the study characterized the effects of each drug on the transcriptome of GCT cells and identified common deregulations in gene expression of ion transporters and DNA-binding factors.
CLINICAL EPIGENETICS
(2022)
Review
Oncology
Jayden Sterling, Sharleen V. Menezes, Ramzi H. Abbassi, Lenka Munoz
Summary: Histone lysine demethylases (KDMs) are enzymes that remove methylation marks on lysines in nucleosomes' histone tails, regulating gene transcription and playing important roles in cancer development. KDMs can have activating or repressing effects on gene transcription, regulating the expression of oncogenes and tumor suppressors.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Chemistry, Medicinal
Martina Menna, Francesco Fiorentino, Biagina Marrocco, Alessia Lucidi, Stefano Tomassi, Domenica Cilli, Mauro Romanenghi, Matteo Cassandri, Silvia Pomella, Michele Pezzella, Donatella Del Bufalo, Mohammad Salik Zeya Ansari, Nevena Tomasevic, Milan Mladenovic, Monica Viviano, Gianluca Sbardella, Rossella Rota, Daniela Trisciuoglio, Saverio Minucci, Andrea Mattevi, Dante Rotili, Antonello Mai
Summary: Chemical modifications of LSD1 led to highly active and selective inhibitors, which showed antiproliferative effects and gene expression regulation in leukemia cells. The inhibition of LSD1 demonstrated a crucial role in solid tumor cells, suggesting no added value for simultaneous G9a inhibition.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Dong-Jun Fu, Jun Li, Bin Yu
Summary: This review highlights the research progress of LSD1 inhibitors, categorizing them into natural and synthetic compounds. The potential of these inhibitors in cancer treatment, as well as related design strategies, are discussed.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Lingling Duan, Yu-An Chen, Yanping Liang, Zhenhua Chen, Jun Lu, Yong Fang, Jiazheng Cao, Jian Lu, Hongwei Zhao, Rey-Chen Pong, Elizabeth Hernandez, Payal Kapur, Tram Anh T. Tran, Tristan Smith, Elisabeth D. Martinez, Jung-Mo Ahn, Jer-Tsong Hsieh, Jun-hang Luo, Zhi-Ping Liu
Summary: Epigenetics is an emerging mechanism for tumorigenesis, and targeting epigenetic regulators has become an attractive strategy for cancer therapy. This study investigated the role of KDM4B in prostate cancer progression and tested the efficacy of the KDM4B inhibitor B3. The results showed that B3 could suppress tumor growth and sensitize tumor cells to anti-androgen receptor antagonists, making it a potential therapeutic agent for castration resistant prostate cancer.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Biochemistry & Molecular Biology
Nicolas L. Young, Ruhee Dere
Summary: Alterations in global epigenetic signatures on chromatin, specifically the overexpression of demethylase KDM4A, play a crucial role in tumor initiation and progression by modulating key cellular processes such as transcription and proliferation. This highlights the therapeutic potential of targeting KDM4A and other demethylases in cancer treatment.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Chunling Ren, Yaolan Lin, Xiaoqin Liu, Dan Yan, Xiao Xu, Dongrong Zhu, Lingyi Kong, Chao Han
Summary: The study isolated four sesquiterpene-based LSD1 inhibitors from zedoary turmeric oil using target separation countercurrent chromatography technique, demonstrating their potential anti-tumor activity.
BIOORGANIC CHEMISTRY
(2021)
Article
Oncology
Chandtip Chandhasin, Van Dang, Frank Perabo, Joselyn Del Rosario, Young K. Chen, Ellen Filvaroff, Jeffrey A. Stafford, Michael Clarke
Summary: The dysregulation of KDM4 has been linked to various cancer processes, and a new pan-inhibitor called TACH101 has shown potent antiproliferative activity and inhibits tumor growth. Additionally, TACH101 reduces the population of tumor-initiating cells.
Review
Pharmacology & Pharmacy
Chang-Yun Li, Yan-Jun Liu, Fan Tao, Ru-Yi Chen, Jin-Jin Shi, Jian-Fei Lu, Guan -Jun Yang, Jiong Chen
Summary: This article discusses the important role of lysine-specific demethylase 7A (KDM7A) in biological regulation and disease development, as well as its structure, function, and potential drug treatments. KDM7A is not only crucial for normal development but also associated with various diseases.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Plant Sciences
Jinghan Zhang, Mengzhen Gu, Chunling Ren, Xiao Xu, Lingyi Kong, Zhongrui Li, Chao Han
Summary: The study found that withanolides, especially withaferin A, can act as LSD1 inhibitors and have potential anti-tumor activity by inhibiting cell migration.
PHYTOCHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Ashley E. Owens, Michael J. Iannotti, Tino W. Sanchez, Ty Voss, Abhijeet Kapoor, Matthew D. Hall, Juan J. Marugan, Sam Michael, Noel Southall, Mark J. Henderson
Summary: Cellular thermal shift assay (CETSA) is a valuable method for confirming target engagement in cellular environment. Traditional CETSA method measures changes in protein thermal stability using immunoblotting, which is low throughput and laborious. This study developed a high-throughput CETSA method that is compatible with 96- and 384-well microplates and removes thermally destabilized proteins using low speed centrifugation. It has been demonstrated to guide structure-activity relationship studies and compound screening.
ACS CHEMICAL BIOLOGY
(2022)
Article
Cell Biology
Christopher Minteer, Marco Morselli, Margarita Meer, Jian Cao, Albert Higgins-Chen, Sabine M. Lang, Matteo Pellegrini, Qin Yan, Morgan E. Levine
Summary: This study demonstrates that physiologically relevant aging changes can be induced in vitro and used to uncover mechanistic insights into epigenetic aging.
Article
Chemistry, Medicinal
Hongmao Sun, Nathan P. Coussens, Carina Danchik, Leah M. Wachsmuth, Mark J. Henderson, Samarjit Patnaik, Matthew D. Hall, Ashley L. Molinaro, Dayle A. Daines, Min Shen
Summary: This study identified potential inhibitors of NTHi VapC1 ribonuclease through virtual screening and scaffold hopping. These inhibitors could serve as starting points for preclinical development.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Yongwang Zhong, Wenjing Yan, Jingjing Ruan, Mike Fang, Changjun Yu, Shaojun Du, Ganesha Rai, Dingyin Tao, Mark J. Henderson, Shengyun Fang
Summary: XBP1 variant 1 (Xv1) is highly expressed in various types of cancer but not in normal tissues. It promotes cancer cell mitosis by upregulating TTLL6 expression, which is essential for spindle formation. This study reveals a new mechanism for Xv1-mediated cancer cell survival.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Daniel R. Scoles, Mandi Gandelman, Sharan Paul, Thomas Dexheimer, Warunee Dansithong, Karla P. Figueroa, Lance T. Pflieger, Scott Redlin, Stephen C. Kales, Hongmao Sun, David Maloney, Robert Damoiseaux, Mark J. Henderson, Anton Simeonov, Ajit Jadhav, Stefan M. Pulst
Summary: CAG repeat expansions in the ATXN2 gene are associated with SCA2 and ALS. Lowering ATXN2 transcription can potentially treat these diseases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Hui Zheng, Lizhen Wu, Qian Xiao, Xin Meng, Alex Hafiz, Qin Yan, Renquan Lu, Jian Cao
Summary: DNA sensing through the cGAS-STING pathway is important in cancer immunosurveillance. Activation of STING in the tumor environment is an attractive approach to induce anti-tumor immunity, but it is limited due to epigenetic silencing of STING in many tumors. In this study, the inhibition of KDM5 family histone demethylases restored STING expression in breast cancer cells and activated the cGAS-STING pathway, showing the potential of KDM5 inhibitors as novel immune modulators in cancer therapies.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Oncology
Goran Micevic, Marcus W. Bosenberg, Qin Yan
Summary: Immune checkpoint inhibitors (ICI) have shown significant improvements in treating various cancers, but there are still challenges to overcome. Some cold tumor types, like pancreatic cancer, have low response rates to ICI due to low immunogenicity. Additionally, patients who initially respond to ICI may experience T-cell exhaustion, leading to a lack of sustained response. Recent studies have highlighted the role of epigenetic modifiers in regulating tumor cell immunity and T-cell exhaustion, suggesting that targeting the intersection of epigenetics and immune checkpoint therapy could enhance antitumor immune responses.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ren Ren, John R. Horton, Qin Chen, Jie Yang, Bin Liu, Yun Huang, Robert M. Blumenthal, Xing Zhang, Xiaodong Cheng
Summary: ZBTB7A is a transcription factor that belongs to a small family with three members in humans. It plays a crucial role in controlling the transcription of various genes, with diverse functions in hematopoiesis, oncogenesis, and metabolism.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
John R. Horton, Jujun Zhou, Qin Chen, Xing Zhang, Mark T. Bedford, Xiaodong Cheng
Summary: The N-terminal half of PHF2 contains a PHD and a Jumonji domain, which can recognize H3 trimethylated at lysine 4 and VRK1. The Jumonji domain can erase dimethylation mark from H3K9me2 at select promoters. The N-terminal half of PHF2 binds to H3 and VRK1 peptides containing K4me3 with higher affinities than the isolated PHD domain.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Genetics & Heredity
Xijuan Liu, Jun Wang, Joshua A. Boyer, Weida Gong, Shuai Zhao, Ling Xie, Qiong Wu, Cheng Zhang, Kanishk Jain, Yiran Guo, Javier Rodriguez, Mingjie Li, Hidetaka Uryu, Chengheng Liao, Lianxin Hu, Jin Zhou, Xiaobing Shi, Yi-Hsuan Tsai, Qin Yan, Weibo Luo, Xian Chen, Brian D. Strahl, Alex von Kriegsheim, Qi Zhang, Gang Greg Wang, Albert S. Baldwin, Qing Zhang
Summary: Histone H3 with hydroxylation of proline at residue 16 (H3P16oh) is an important histone post-translational modification (PTM) in mammalian cells, and it regulates mammalian gene expression.
Article
Biochemistry & Molecular Biology
Quinlin M. Hanson, Nate Hoxie, Min Shen, Hui Guo, Ig-Jun Cho, Ipsita Chakraborty, Brooklyn M. Aragon, Ganesha Rai, Samarjit Patnaik, John S. Janiszewski, Matthew D. Hall
Summary: Target class profiling (TCP) is a chemistry biology approach used to investigate understudied biological targets. By developing a generalizable assay platform and screening curated compound libraries, TCP explores the chemical biological space of enzyme families. In this study, TCP was used to investigate inhibitory activity in a set of small-molecule methyltransferases (SMMTases) in order to explore this relatively unexplored target class. High-throughput screening (HTS)-amenable assays were optimized to screen a large number of small molecules against representative SMMTases, resulting in the identification of a novel inhibitor for the SMMTase HNMT.
ACS CHEMICAL BIOLOGY
(2023)
Article
Genetics & Heredity
Jin Wei, Ajinkya Patil, Clayton K. Collings, Mia Madel Alfajaro, Yu Liang, Wesley L. Cai, Madison S. Strine, Renata B. Filler, Peter C. DeWeirdt, Ruth E. Hanna, Bridget L. Menasche, Arya Okten, Mario A. Pena-Hernandez, Jon Klein, Andrew McNamara, Romel Rosales, Briana L. McGovern, M. Luis Rodriguez, Adolfo Garcia-Sastre, Kris M. White, Yiren Qin, John G. Doench, Qin Yan, Akiko Iwasaki, Thomas P. Zwaka, Jun Qi, Cigall Kadoch, Craig B. Wilen
Summary: This study demonstrates that the activity of the chromatin remodeling complex mSWI/SNF plays an important role in determining susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, highlighting it as a potential therapeutic target for SARS-CoV-2.
Article
Biochemistry & Molecular Biology
Quinlin M. Hanson, Nate Hoxie, Min Shen, Hui Guo, Ig-Jun Cho, Ipsita Chakraborty, Brooklyn M. Aragon, Ganesha Rai, Samarjit Patnaik, John S. Janiszewski, Matthew D. Hall
Summary: Target class profiling (TCP) is a chemical biology approach to investigate understudied biological target classes. In this study, TCP was used to investigate inhibitory activity of small-molecule methyltransferases (SMMTases), and a novel inhibitor was discovered for the SMMTase HNMT.
ACS CHEMICAL BIOLOGY
(2023)
Article
Oncology
Gang Peng, Yibo Xi, Chiara Bellini, Kien Pham, Zhen W. Zhuang, Qin Yan, Man Jia, Guilin Wang, Lingeng Lu, Moon-Shong Tang, Hongyu Zhao, He Wang
Summary: Epigenomic-wide DNA methylation profiling has the potential to reflect risks associated with electronic cigarette exposure and individual poor health outcomes. Our study in male ApoE-/- mice reveals significant alterations in CpG sites after electronic cigarette exposure, with a high percentage annotated with known genes. Pathway analysis indicates activation of MAPK and cardiomyocyte-related signaling pathways, suggesting potential cell-damaging effects of prolonged e-cigarette inhalation.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Chemistry, Medicinal
Guangping Dong, Youchao Deng, Adam Yasgar, Ravi Yadav, Daniel Talley, Alexey Zakharov, Sankalp Jain, Ganesha Rai, Nicholas Noinaj, Anton Simeonov, Rong Huang
Summary: Venglustat has been identified as a potent inhibitor of NTMT1 with competitive binding at the peptide substrate site. This study reveals the importance of quinuclidine and fluorophenyl parts of Venglustat for NTMT1 inhibition. The research sheds light on NTMT1's biological roles and provides insights for future clinical investigations.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)