Review
Biochemistry & Molecular Biology
Ji Hye Kim, Byong Chul Yoo, Woo Seok Yang, Eunji Kim, Sungyoul Hong, Jae Youl Cho
Summary: Cells have developed a sophisticated signaling pathway in response to DNA damage, with protein arginine methylation playing critical roles in modulating DNA repair proteins and maintaining genome integrity. PRMTs can directly methylate DNA repair proteins or deposit methylation marks on histones to regulate various cellular processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Annika Schmidt, Jana Frei, Ansgar Poetsch, Alexandra Chittka, Hui Zhang, Chris Assmann, Anne Lehmkuhl, Uta-Maria Bauer, Ulrike A. Nuber, M. Cristina Cardoso
Summary: This study identified and validated novel post-translational modifications of MeCP2 in the brain, showing that these modifications can modulate its ability to bind to and reorganize heterochromatin, which may play a role in the pathology of Rett syndrome.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Iredia D. Iyamu, Ayad A. Al-Hamashi, Rong Huang
Summary: In this study, a potent pan-inhibitor II757 for PRMTs was designed and synthesized, showing high inhibition for various PRMTs and competitively binding at the SAM binding site of PRMT1. II757 also exhibited selectivity for PRMTs over other methyltransferases, serving as a general probe and a lead for further optimization.
Article
Neurosciences
Kewei Chang, Dan Gao, Jidong Yan, Liyan Lin, Tingting Cui, Shemin Lu
Summary: Arginine methylation, mediated by arginine methyltransferases and demethylases, plays crucial roles in cellular processes and has been linked to various diseases. This review provides an overview of the biochemistry and regulatory mechanism of arginine methylation, with a focus on its roles in the central nervous system and neurological diseases.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Oncology
Yu Lei, Ping Han, Dean Tian
Summary: Hepatocellular carcinoma (HCC) is a highly prevalent cancer with complex initiation and progression, posing challenges for diagnosis and treatment. Research on the emerging roles of protein arginine methylation in cancers, particularly the family of protein arginine methyltransferases (PRMTs), is growing. The dysregulation of PRMTs in cancers, including HCC, is being uncovered, with potential applications in therapy being explored through PRMT inhibitors.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Zhenhua Li, Jingping Xu, Yao Song, Chong Xin, Lantao Liu, Ning Hou, Yan Teng, Xuan Cheng, Tianle Wang, Zhenyang Yu, Jiangping Song, Youyi Zhang, Jian Wang, Xiao Yang
Summary: This study reveals a crucial role of PRMT5 in regulating protein O-GlcNAcylation by increasing levels of O-GlcNAcylation in the heart through suppressing OGA expression and triggering aberrant splicing, leading to DCM. Targeting the PRMT5-OGA axis could be a potential therapeutic strategy for treating DCM.
CIRCULATION RESEARCH
(2021)
Article
Oncology
Renyong Zhi, Kailiang Wu, Jingyue Zhang, Hanjiao Liu, Chen Niu, Shuai Li, Li Fu
Summary: Invasive micropapillary carcinoma (IMPC) is a subtype of breast cancer with higher incidence of lymphovascular invasion and lymph node metastasis compared to invasive ductal carcinoma (IDC). Through metabolomics analysis, the study identified distinct metabolic profiles in IMPC characterized by high levels of arginine methylation marks. The critical regulator PRMT3, responsible for catalyzing the formation of these marks, was found to be overexpressed in IMPC and associated with poor prognosis. Inhibition of PRMT3 activity showed potential as a treatment for breast cancer.
Review
Chemistry, Medicinal
Jinyun Dong, Jilong Duan, Zi Hui, Carmen Garrido, Zhangshuang Deng, Tian Xie, Xiang-Yang Ye
Summary: Protein arginine methyltransferases (PRMTs), enzymes that methylate target proteins, are crucial for maintaining normal physiological function. Abnormal expressions and enhanced activities of PRMTs are closely associated with various diseases. The development of PRMT inhibitors has attracted significant attention for research in cancer therapy. This review focuses on small-molecule inhibitors targeting PRMTs, particularly PRMT5 inhibitors, and discusses their clinical development. The development of new, effective inhibitors with isoform-specific and tumor-biased distributions is an important area for further study.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2022)
Review
Endocrinology & Metabolism
Lucie Malbeteau, Ha Thuy Pham, Louisane Eve, Michael R. Stallcup, Coralie Poulard, Muriel Le Romancer
Summary: Steroid receptors (SRs) are important members of the nuclear hormonal receptor family, regulating various physiological functions essential for human health. Dysregulation of SRs may contribute to a wide range of pathologies, highlighting the significance of understanding their regulatory mechanisms.
Article
Cell Biology
Yi Liu, Hejing Liu, Miaomiao Ye, Mengying Jiang, Xin Chen, Gendi Song, Huihui Ji, Zhi-wei Wang, Xueqiong Zhu
Summary: This study reveals that BRD4, a member of the BET protein family, is asymmetrically methylated by PRMT1 in ovarian cancer. The overexpression of PRMT1 is associated with poor prognosis in ovarian cancer patients. Silencing PRMT1 inhibits ovarian cancer proliferation, migration, and invasion. PRMT1-mediated BRD4 methylation promotes BRD4 phosphorylation and is involved in ovarian cancer metastasis.
CELL DEATH & DISEASE
(2023)
Review
Biochemical Research Methods
Carlos H. M. Rodrigues, Douglas E. Pires, Tom L. Blundell, David B. Ascher
Summary: Protein-protein interfaces have unique binding geometry and physicochemical properties, with concave binding sites that challenge the previous belief about their flatness. A comprehensive review of protein-protein interface landscape reveals the utilization of small binding pockets even in larger flat interfaces.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Parasitology
Mario Alberto Rodriguez
Summary: Arginine methylation is a post-translational modification that plays a significant role in protozoan parasites, particularly in pathogenicity-related events. Several PRMTs have been identified in these parasites and are involved in cell growth, stress response, stage transitions, and virulence.
Review
Immunology
Weijing Dai, Jianguo Zhang, Siqi Li, Fajian He, Qiao Liu, Jun Gong, Zetian Yang, Yan Gong, Fang Tang, Zhihao Wang, Conghua Xie
Summary: Protein arginine methyltransferases (PRMTs) have emerged as a new family of gene expression regulators in eukaryotes, and they are associated with cancer pathogenesis and progression. Protein arginine methylation plays important roles in cancer immunity and the regulation of immunotherapy efficacy. This review summarizes the latest information on regulatory molecular mechanisms and different arginine methylation signaling pathways in innate and adaptive immune responses during cancer, and highlights the potential of PRMT inhibitors as effective combinatorial treatments with immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Jianjun Yu, Chao Yu, Georgia Bayliss, Shougang Zhuang
Summary: Protein arginine methyltransferases (PRMTs) regulate gene transcription and post-translational modifications by methylating a range of histone and non-histone substrates, participating in multiple biological processes. While most studies have focused on their roles in tumors and other organs, there is emerging evidence that PRMTs are expressed in the kidney and contribute to renal development, injury, repair, and fibrosis. This review summarizes the role and mechanisms of PRMTs in regulating these renal processes and provides a perspective for future clinical applications.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Charles Brobbey, Shasha Yin, Liu Liu, Lauren E. Ball, Philip H. Howe, Joe R. Delaney, Wenjian Gan
Summary: Protein arginine methyltransferase 5 (PRMT5) catalyzes methylation on arginine residues and has potential as an antitumor target. This study shows that autophagy blockage increases the sensitivity of triple negative breast cancer cells to PRMT5 inhibitor. PRMT5 mediates autophagy by methylating ULK1, and inhibition of ULK1 enhances the therapeutic effect of PRMT5 inhibitor. These findings suggest the combination of PRMT5 and autophagy inhibitors as a potential strategy in cancer therapy.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Medicinal
Jorge A. N. Santos, Marcia Y. Kondo, Renato F. Freitas, Marcelo H. dos Santos, Teodorico C. Ramalho, Diego M. Assis, Luiz Juliano, Maria A. Juliano, Luciano Puzer
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2016)
Article
Chemistry, Medicinal
Renato Ferreira de Freitas, Mohammad S. Eram, David Smil, Magdalena M. Szewczyk, Steven Kennedy, Peter J. Brown, Vijayaratnam Santhakumar, Dalia Barsyte-Lovejoy, Cheryl H. Arrowsmith, Masoud Vedadi, Matthieu Schapira
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Yudao Shen, Magdalena M. Szewczyk, Mohammad S. Eram, David Smil, H. Umit Kaniskan, Renato Ferreira de Freitas, Guillermo Senisterra, Fengling Li, Matthieu Schapira, Peter J. Brown, Cheryl H. Arrowsmith, Dalia Barsyte-Lovejoy, Jing Liu, Masoud Vedadi, Jian Jin
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Renato Ferreira de Freitas, Mohammad S. Eram, Magdalena M. Szewczyk, Holger Steuber, David Smil, Hong Wu, Fengling Li, Guillermo Senisterra, Aiping Dong, Peter J. Brown, Marion Hitchcock, Dieter Moosmayer, Christian M. Stegmann, Ursula Egner, Cheryl Arrowsmith, Dalia Barsyte-Loyejoy, Masoud Vedadi, Matthieu Schapira
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Rachel J. Harding, Renato Ferreira de Freitas, Patrick Collins, Ivan Franzoni, Mani Ravichandran, Hui Ouyang, Kevin A. Juarez-Ornelas, Mark Lautens, Matthieu Schapira, Frank von Delft, Vjayaratnam Santhakumar, Cheryl H. Arrowsmith
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Renato Ferreira de Freitas, Matthieu Schapira
Article
Chemistry, Medicinal
Renato Ferreira de Freitas, Rachel J. Harding, Ivan Franzoni, Mani Ravichandran, Mandeep K. Mann, Hui Ouyang, Mark Lautens, Vijayaratnam Santhakumar, Cheryl H. Arrowsmith, Matthieu Schapira
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Pavel Mader, Rodrigo Mendoza-Sanchez, Aman Iqbal, Aiping Dong, Elena Dobrovetsky, Victoria B. Corless, Sean K. Liew, Scott R. Houliston, Renato Ferreira De Freitas, David Smil, Carlo C. Dela Sena, Steven Kennedy, Diego B. Diaz, Hong Wu, Ludmila Dombrovski, Abdellah Allali-Hassani, Jinrong Min, Matthieu Schapira, Masoud Vedadi, Peter J. Brown, Vijayaratnam Santhakumar, Andrei K. Yudin, Cheryl H. Arrowsmith
BIOORGANIC & MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Alexandria P. Taylor, Magdalena Swewczyk, Steven Kennedy, Viacheslav V. Trush, Hong Wu, Hong Zeng, Aiping Dong, Renato Ferreira de Freitas, John Tatlock, Robert A. Kumpf, Martin Wythes, Agustin Casimiro-Garcia, Rajiah Aldrin Denny, Mihir D. Parikh, Fengling Li, Dalia Barsyte-Lovejoy, Matthieu Schapira, Masoud Vedadi, Peter J. Brown, Cheryl H. Arrowsmith, Dafydd R. Owen
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Mandeep K. Mann, Ivan Franzoni, Renato Ferreira de Freitas, Wolfram Tempel, Scott Houliston, Leanna Smith, Masoud Vedadi, Cheryl H. Arrowsmith, Rachel J. Harding, Matthieu Schapira
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Review
Biochemistry & Molecular Biology
Renato Ferreira de Freitas, Danton Ivanochko, Matthieu Schapira
Article
Chemistry, Medicinal
Renato Ferreira de Freitas, Yanli Liu, Magdalena M. Szewczyk, Naimee Mehta, Fengling Li, David McLeod, Carlos Zepeda-Velazquez, David Dilworth, Ronan P. Hanley, Elisa Gibson, Peter J. Brown, Rima Al-Awar, Lindsey James, Cheryl H. Arrowsmith, Dalia Barsyte-Lovejoy, Jinrong Min, Masoud Vedadi, Matthieu Schapira, Abdellah Allali-Hassani
Summary: This study identified the first antagonist that blocks the interaction between NSD2 and H3K36me2, providing a potential new approach for targeting NSD2 and further understanding its cellular function.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
David Dilworth, Ronan P. Hanley, Renato Ferreira de Freitas, Abdellah Allali-Hassani, Mengqi Zhou, Naimee Mehta, Matthew R. Marunde, Suzanne Ackloo, Raquel Arminda Carvalho Machado, Aliakbar Khalili Yazdi, Dominic D. G. Owens, Victoria Vu, David Y. Nie, Mona Alqazzaz, Edyta Marcon, Fengling Li, Irene Chau, Albina Bolotokova, Su Qin, Ming Lei, Yanli Liu, Magdalena M. Szewczyk, Aiping Dong, Sina Kazemzadeh, Tigran Abramyan, Irina K. Popova, Nathan W. Hall, Matthew J. Meiners, Marcus A. Cheek, Elisa Gibson, Dmitri Kireev, Jack F. Greenblatt, Michael-C Keogh, Jinrong Min, Peter J. Brown, Masoud Vedadi, Cheryl H. Arrowsmith, Dalia Barsyte-Lovejoy, Lindsey James, Matthieu Schapira
Summary: NSD2 is an enzyme responsible for dimethylation of lysine 36 of histone 3, with multiple domains involved in chromatin reading. The chemical probe UNC6934 can modulate NSD2 activity and localization, affecting cellular functions.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wemenes Jose Lima Silva, Renato Ferreira de Freitas
Summary: This study investigates the accuracy and efficiency of different computational methods and protocols to predict the free energy of binding for a series of KLK6 inhibitors. The results show that the performance of the methods varied strongly depending on the system. The free energy perturbation (FEP) method showed improved binding affinity predictions and ranked the most potent compounds at the top of the list in a simulation of a real-world drug discovery project.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2023)
Article
Chemistry, Medicinal
Rachel J. Harding, Ivan Franzoni, Mandeep K. Mann, Magdalena M. Szewczyk, Bijan Mirabi, Renato Ferreira de Freitas, Dominic D. G. Owens, Suzanne Ackloo, Alexej Scheremetjew, Kevin A. Juarez-Ornelas, Randy Sanichar, Rachel J. Baker, Christian Dank, Peter J. Brown, Dalia Barsyte-Lovejoy, Vijayaratnam Santhakumar, Matthieu Schapira, Mark Lautens, Cheryl H. Arrowsmith
Summary: Inhibition of HDAC6-UBD is a promising strategy for treating cancers, and a potent chemical probe SGC-UBD253 (25) has been developed for targeting HDAC6-UBD. A methylated derivative SGC-UBD253N (32) was also identified as a negative control. These findings provide insights into the biological function of HDAC6-UBD and the therapeutic potential of targeting this domain.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)