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
Multidisciplinary Sciences
Fan Chen, Aria L. L. Byrd, Jinpeng Liu, Robert M. M. Flight, Tanner J. J. DuCote, Kassandra J. J. Naughton, Xiulong Song, Abigail R. R. Edgin, Alexsandr Lukyanchuk, Danielle T. T. Dixon, Christian M. M. Gosser, Dave-Preston Esoe, Rani D. D. Jayswal, Stuart H. H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson
Summary: The impact of EZH2 deficiency on KRAS-driven lung adenocarcinomas was studied, and it was found that haplo-insufficiency and full-insufficiency of EZH2 have divergent effects. Tumors with EZH2 haplo-insufficiency were less lethal and lower grade compared to tumors with EZH2 full-insufficiency. Three-dimensional cultures were used to explore epigenetic drug sensitivities for cancer.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Yuan Sui, Ruicai Gu, Ralf Janknecht
Summary: Epigenetic changes in cancer development often involve dysregulation of enzymes modifying DNA or histones, with JMJD1 proteins playing a key role as histone lysine demethylases. The JMJD1 subfamily, including JMJD1A, JMJD1B, and JMJD1C, have been shown to have significant impact on tumorigenesis through regulation of gene expression and oncogene activation. While JMJD1A and JMJD1C are often overexpressed in tumors and promote cancer growth, JMJD1B may exhibit tumor suppressive functions in certain cancers.
MOLECULAR CANCER RESEARCH
(2021)
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)
Article
Oncology
Ruicai Gu, Tae-Dong Kim, Hanlin Jiang, Sook Shin, Sangphil Oh, Ralf Janknecht
Summary: This study reveals the regulatory mechanism of JMJD2D through lysine methylation. The mutation of lysine residue reduces the growth and invasion ability of prostate cancer cells and leads to transcriptomic changes. In addition, CBLC expression is elevated in prostate tumors, and its downregulation mimics the effects of the K427 mutation in JMJD2D.
FRONTIERS IN ONCOLOGY
(2023)
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)
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
Oncology
Pedro A. Lazo
Summary: Chromatin remodeling plays a crucial role in tumor biology. Targeting epigenetic enzymes and chromatin kinases can be a novel strategy for cancer treatment. Targeting these enzymes can enhance tumor cell sensitivity to treatment and improve treatment outcomes.
Article
Immunology
Dorota Iwaszkiewicz-Grzes, Magdalena Piotrowska, Mateusz Gliwinski, Zuzanna Urban-Wojciuk, Piotr Trzonkowski
Summary: The study revealed that insulin beta chain peptide 9-23 favored specific Tregs expression, while whole insulin activated both Tregs and Teffs. Tregs SPECB:9-23 showed the highest level of expression in crucial genes and lower methylation levels.
FRONTIERS IN IMMUNOLOGY
(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)
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
Immunology
Jingjing Wang, Zhikai Wu, Xingyi Zhu, Peixuan Li, Yiwu Fu, Xia Wang, Youpeng Sun, Ershun Zhou, Zhengtao Yang
Summary: The study demonstrates the important regulatory roles of LSD1 in LPS-induced mastitis and the inhibitory effects of GSK-LSD1 on LSD1 activity, leading to reduced inflammatory response and tissue damage. The inhibition of LSD1 results in increased histone H3K4me2 and H3K9me2 levels, and suppression of NF-kappa B signaling and cytokine production in mammary gland. These findings suggest LSD1 as a potential regulator of inflammation and provide insights into epigenetic control mechanisms in inflammation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
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
Plant Sciences
Seong Woo Noh, Ri-Ra Seo, Hee Jin Park, Ho Won Jung
Summary: LDL1 and LDL2 play important roles in Arabidopsis immunity by maintaining histone methylation and enhancing resistance to Pseudomonas syringae. Double mutants ldl1 ldl2 show more stable transcription of defense-related genes and disease resistance responses. This study suggests that LDL1 and LDL2 regulate the transcriptional sensitivity of defense genes to establish a primed defense response.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Clinical Neurology
Lea M. Stitzlein, Achintyan Gangadharan, Leslie M. Walsh, Deokhwa Nam, Alexsandra B. Espejo, Melissa M. Singh, Kareena H. Patel, Yue Lu, Xiaoping Su, Ravesanker Ezhilarasan, Joy Gumin, Sanjay Singh, Erik Sulman, Frederick F. Lang, Joya Chandra
Summary: In this study, the efficacy of LSD1 inhibitors in patient-derived glioblastoma stem cell (GSC) models was evaluated. The results showed that LSD1 inhibitors had selective cytotoxic effects, but tumor regrowth occurred. Genes that may predict resistance to LSD1 inhibitors were identified using RNA-seq, providing guidance for future combination therapies.
FRONTIERS IN NEUROLOGY
(2023)
Article
Chemistry, Medicinal
Daisuke Ogasawara, Taka-Aki Ichu, Hui Jing, Jonathan J. Hulce, Alex Reed, Olesya A. Ulanovskaya, Benjamin F. Cravatt
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Zhen Chen, Wakana Mori, Xiaoyun Deng, Ran Cheng, Daisuke Ogasawara, Genwei Zhang, Michael A. Schafroth, Kenneth Dahl, Hualong Fu, Akiko Hatori, Tuo Shao, Yiding Zhang, Tomoteru Yamasaki, Xiaofei Zhang, Jian Rong, Qngzhen Yu, Kuan Hu, Masayuki Fujinaga, Lin Xie, Katsushi Kumata, Yuancheng Gou, Jingjin Chen, Shuyin Gu, Liang Bao, Lu Wang, Thomas Lee Collier, Neil Vasdev, Yihan Shao, Jun-An Ma, Benjamin F. Cravatt, Christopher Fowler, Lee Josephson, Ming-Rong Zhang, Steven H. Liang
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Zhen Chen, Wakana Mori, Hualong Fu, Michael A. Schafroth, Akiko Hatori, Tuo Shao, Genwei Zhang, Richard S. Van, Yiding Zhang, Kuan Hu, Masayuki Fujinaga, Lu Wang, Vasily Belov, Daisuke Ogasawara, Pilar Giffening, Xiaoyun Deng, Jian Rong, Qingzhen Yu, Xiaofei Zhang, Mikhail I. Papisov, Yihan Shao, Thomas L. Collier, Jun-An Ma, Benjamin F. Cravatt, Lee Josephson, Ming-Rong Zhang, Steven H. Ling
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Review
Pharmacology & Pharmacy
Daisuke Ogasawara
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
(2020)
Article
Biochemistry & Molecular Biology
Taka-Aki Ichu, Alex Reed, Daisuke Ogasawara, Olesya Ulanovskaya, Amanda Roberts, Carlos A. Aguirre, Liron Bar-Peled, Jie Gao, Jason Germain, Sabrina Barbas, Kim Masuda, Bruno Conti, Peter Tontonoz, Benjamin F. Cravatt
Article
Biochemistry & Molecular Biology
Elliot D. Mock, Mohammed Mustafa, Ozge Gunduz-Cinar, Resat Cinar, Gavin N. Petrie, Vasudev Kantae, Xinyu Di, Daisuke Ogasawara, Zoltan V. Varga, Janos Paloczi, Cristina Miliano, Giulia Donvito, Annelot C. M. van Esbroeck, Anouk M. F. van der Gracht, Ioli Kotsogianni, Joshua K. Park, Andrea Martella, Tom van der Wel, Marjolein Soethoudt, Ming Jiang, Tiemen J. Wendel, Antonius P. A. Janssen, Alexander T. Bakker, Colleen M. Donovan, Laura Castillo, Bogdan Florea, Jesse Wat, Helma van den Hurk, Matthias Wittwer, Uwe Grether, Andrew Holmes, Constant A. A. van Boeckel, Thomas Hankemeier, Benjamin F. Cravatt, Matthew W. Buczynski, Matthew N. Hill, Pal Pacher, Aron H. Lichtman, Mario van der Stelt
NATURE CHEMICAL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Bernard P. Kok, Srijana Ghimire, Woojoo Kim, Shreyosree Chatterjee, Tyler Johns, Seiya Kitamura, Jerome Eberhardt, Daisuke Ogasawara, Janice Xu, Ara Sukiasyan, Sean M. Kim, Cristina Godio, Julia M. Bittencourt, Michael Cameron, Andrea Galmozzi, Stefano Forli, Dennis W. Wolan, Benjamin F. Cravatt, Dale L. Boger, Enrique Saez
NATURE CHEMICAL BIOLOGY
(2020)
Article
Ophthalmology
Sally Miller, Laura Daily, Vijai Dharla, Juerg Gertsch, Michael S. Malamas, Iwao Ojima, Martin Kaczocha, Daisuke Ogasawara, Alex Straiker
EXPERIMENTAL EYE RESEARCH
(2020)
Article
Chemistry, Medicinal
Lu Hou, Jian Rong, Ahmed Haider, Daisuke Ogasawara, Cassis Varlow, Michael A. Schafroth, Linjing Mu, Jiefeng Gan, Hao Xu, Christopher J. Fowler, Ming-Rong Zhang, Neil Vasdev, Simon Ametamey, Benjamin F. Cravatt, Lu Wang, Steven H. Liang
Summary: The endocannabinoid system (ECS) plays a crucial role in various biological functions, including cannabinoid receptors and enzymes responsible for endocannabinoid synthesis and degradation. Significant progress has been made in developing PET tracers targeting different components of the ECS, particularly for neuroimaging applications. The review discusses the development of state-of-the-art PET tracers for the ECS, including their chemical design, pharmacological properties, radiolabeling, and imaging applications.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Zhen Chen, Wakana Mori, Jian Rong, Michael A. Schafroth, Tuo Shao, Richard S. Van, Daisuke Ogasawara, Tomoteru Yamasaki, Atsuto Hiraishi, Akiko Hatori, Jiahui Chen, Yiding Zhang, Kuan Hu, Masayuki Fujinaga, Jiyun Sun, Qingzhen Yu, Thomas L. Collier, Yihan Shao, Benjamin F. Cravatt, Lee Josephson, Ming-Rong Zhang, Steven H. Liang
Summary: MAGL inhibitors show promise in treating various CNS disorders, and the design and synthesis of MAGL PET probes are crucial for the development of these drugs.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Chemistry, Medicinal
Jian Rong, Wakana Mori, Xiaotian Xia, Michael A. Schafroth, Chunyu Zhao, Richard S. Van, Tomoteru Yamasaki, Jiahui Chen, Zhiwei Xiao, Ahmed Haider, Daisuke Ogasawara, Atsuto Hiraishi, Tuo Shao, Yiding Zhang, Zhen Chen, Fuwen Pang, Kuan Hu, Lin Xie, Masayuki Fujinaga, Katsushi Kumata, Yuancheng Gou, Yang Fang, Shuyin Gu, Huiyi Wei, Liang Bao, Hao Xu, Thomas L. Collier, Yihan Shao, Richard E. Carson, Benjamin F. Cravatt, Lu Wang, Ming-Rong Zhang, Steven H. Liang
Summary: Monoacylglycerol lipase (MAGL) is responsible for hydrolyzing 2-arachidonoylglycerol into arachidonic acid in the central nervous system, making it a potential target for treating psychiatric disorders and neurodegenerative diseases. Reversible MAGL inhibitors were designed and synthesized, with compounds 10 and 15 identified as the best performers. Radiolabeling with fluorine-18 and evaluation in rodents and nonhuman primates showed that compound [F-18]15 demonstrated the best performance as a PET radioligand for visualizing MAGL in the brain.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Ran Cheng, Masayuki Fujinaga, Jing Yang, Jian Rong, Ahmed Haider, Daisuke Ogasawara, Richard S. Van, Tuo Shao, Zhen Chen, Xiaofei Zhang, Erick R. Calderon Leon, Yiding Zhang, Wakana Mori, Katsushi Kumata, Tomoteru Yamasaki, Lin Xie, Shaofa Sun, Lu Wang, Chongzhao Ran, Yihan Shao, Benjamin Cravatt, Lee Josephson, Ming-Rong Zhang, Steven H. Liang
Summary: MAGL is a key enzyme involved in regulating endocannabinoid balance by degrading 2-AG, and selective inhibition of it may have therapeutic implications for various pathologies. A reversible and peripheral-specific radiofluorinated MAGL PET ligand has been developed, showing exceptional specificity and selectivity in BAT, providing a non-invasive imaging tool for studying the role of BAT in ECS-related pathologies.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Zhengyuan Pang, Michael A. Schafroth, Daisuke Ogasawara, Yu Wang, Victoria Nudell, Neeraj K. Lal, Dong Yang, Kristina Wang, Dylan M. Herbst, Jacquelyn Ha, Carlos Guijas, Jacqueline L. Blankman, Benjamin F. Cravatt, Li Ye
Summary: This study develops a clearing-assisted tissue click chemistry (CATCH) technique for optically imaging covalent drug targets in intact mammalian tissues. The researchers find that CATCH enables specific and robust imaging of target-bound drug molecules at subcellular resolution, and it can also identify the target cell types. By using inhibitors of endocannabinoid hydrolases and monoamine oxidases, the study not only reveals distinct anatomical distributions and predominant cell targets of different drug compounds in the mouse brain, but it also uncovers unexpected differences in drug engagement across and within brain regions, reflecting rare cell types and dose-dependent target shifts that cannot be accessed by conventional methods.
Article
Clinical Neurology
Matthew N. Bainbridge, Aloran Mazumder, Daisuke Ogasawara, Rami Abou Jamra, Genevieve Bernard, Enrico Bertini, Lydie Burglen, Heidi Cope, Ali Crawford, Alexa Derksen, Leon Dure, Emily Gantz, Margarete Koch-Hogrebe, Anna C. E. Hurst, Sonal Mahida, Paige Marshall, Alessia Micalizzi, Antonio Novelli, Hongfan Peng, Diana Rodriguez, Shira L. Robbins, S. Lane Rutledge, Roberta Scalise, Sophia Schliesske, Vandana Shashi, Siddharth Srivastava, Isabella Thiffault, Sarah Topol, Leila Qebibo, Dagmar Wieczorek, Benjamin Cravatt, Svasti Haricharan, Ali Torkamani, Jennifer Friedman
Summary: Mutation of the endocannabinoid gene DAGLA causes a pediatric syndrome characterized by developmental delay, ataxia, and abnormal head and eye movements. The truncated protein may be mislocalized, leading to the observed phenotype. This study highlights the first direct link between an endocannabinoid system component and human genetic disease.
Meeting Abstract
Ophthalmology
Guoqin Wei, Shreyosree Chatterjee, Sanahan Vijayakumar, Daisuke Ogasawara, Yoichiro Ideguchi, Edith Aguilar, Sarah Giles, Dale Boger, Benjamin Cravatt, Michael J. Sailor, Martin Friedlander
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
