Article
Medicine, Research & Experimental
Federica Corrao, Maria Grazia Zizzo, Marco Tutone, Raffaella Melfi, Ignazio Fiduccia, Pietro Salvatore Carollo, Aldo Di Leonardo, Gaetano Caldara, Riccardo Perriera, Andrea Pace, Beatrice Belmonte, Selene Sammataro, Ivana Pibiri, Laura Lentini
Summary: This study investigated the acute toxicological effects of three Translational Readthrough Inducing Drugs (TRIDs) on mice and found that these drugs showed good tolerability without causing significant adverse effects in the mice.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Riccardo Perriera, Emanuele Vitale, Ivana Pibiri, Pietro Salvatore Carollo, Davide Ricci, Federica Corrao, Ignazio Fiduccia, Raffaella Melfi, Maria Grazia Zizzo, Marco Tutone, Andrea Pace, Laura Lentini
Summary: Nonsense mutations cause genetic diseases, but translational readthrough-inducing drugs (TRIDs) offer a promising approach to correct these defects. The new TRIDs NV848, NV914, and NV930 have been shown to restore protein synthesis without affecting natural termination codons (NTCs).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Sandra Luna, Leire Torices, Janire Mingo, Laura Amo, Isabel Rodriguez-Escudero, Pablo Ruiz-Ibarlucea, Asier Erramuzpe, Jesus M. Cortes, Maria I. Tejada, Maria Molina, Caroline E. Nunes-Xavier, Jose I. Lopez, Victor J. Cid, Rafael Pulido
Summary: The PTEN tumor suppressor gene is frequently mutated in tumors and in cancer predisposition patients or those with macrocephaly associated with autism. A study has analyzed PTEN nonsense mutations and set standards for the potential restoration of full-length PTEN proteins from mutated PTEN genes through translational readthrough. The findings indicate that prevalent pathogenic PTEN mutations can be functionally restored through readthrough-inducing compounds, offering potential for precision interventions in specific patient groups.
Review
Biochemistry & Molecular Biology
Patricia Martins-Dias, Luisa Romao
Summary: Nonsense mutations can lead to dysfunctional proteins, but nonsense suppression therapy has the potential to restore protein function and treat a variety of genetic disorders. However, the efficiency of suppression may be influenced by nonsense-mediated decay, highlighting the importance of using NMD inhibitors or readthrough-compound potentiators to enhance therapeutic effects.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mikel D. D. Ghelfi, Saleem Y. Y. Bhat, Hong Li, Barry S. S. Cooperman
Summary: The research findings show that Ataluren acts as a competitive inhibitor, blocking the catalytic function of the release factor complex (RFC) and inducing readthrough. This opens up the possibility of discovering new readthrough-inducing drugs that are both low in toxicity and more effective at stimulating readthrough.
Article
Biology
Martine Palma, Fabrice Lejeune
Summary: Recognition of the stop codon is crucial for terminating translation and synthesizing the correct size protein. Stop codon readthrough can occur under specific conditions, leading to different protein isoforms, and has potential therapeutic implications for genetic diseases caused by nonsense mutations.
BIOLOGICAL REVIEWS
(2021)
Article
Chemistry, Medicinal
Christie Morrill, Westley J. Friesen, Suresh Babu, Ramil Y. Baiazitov, Wu Du, Diane B. Karloff, Chang -Sun Lee, Young-Choon Moon, Hongyu Ren, Jairo Sierra, Yuki Tomizawa, Priya Vazirani, Ellen M. Welch, Xiaojiao Xue, Jin Zhuo
Summary: Using small molecules to induce readthrough is an effective method for treating genetic diseases and cancers. This study introduces a series of novel compounds that show potential for inducing readthrough in cells, either as combination therapy or standalone treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Shan Li, Juan Li, Wenjing Shi, Ziyan Nie, Shasha Zhang, Fengdie Ma, Jun Hu, Jianjun Chen, Peiqiang Li, Xiaodong Xie
Summary: This review summarizes the pharmacodynamics and clinical application potential of the main translational readthrough-inducing drugs (TRIDs) discovered so far, especially some newly discovered TRIDs in the past decade. The discovery of these TRIDs brings hope for treating nonsense mutations in various genetic diseases. Further research is still needed to deeply understand the mechanism of eukaryotic cell termination and drug-induced PTC readthrough so that patients can achieve the greatest benefit from the various TRID treatments.
Article
Chemistry, Medicinal
Shota Kawai, Shunsuke Takashima, Masafumi Ando, Sayaka Shintaku, Shigemitsu Takeda, Kazuya Otake, Yuma Ito, Masaki Fukui, Megumi Yamamoto, Yoshimichi Shoji, Hiroaki Shirahase, Tatsuya Kitao
Summary: The novel triaryl derivative KY-516 exhibits potent readthrough-inducing activity and has potential as a therapeutic agent for Hurler syndrome, according to this study.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2023)
Article
Biochemistry & Molecular Biology
Venkateshwar Mutyam, Jyoti Sharma, Yao Li, Ning Peng, Jianguo Chen, Li Ping Tang, Emily Falk Libby, Ashvani K. Singh, Katja Conrath, Steven M. Rowe
Summary: Premature-termination codons (PTCs) in the CFTR gene lead to nonfunctional CFTR protein, accounting for 11% of CF-causing alleles with no current effective treatments. Novel CFTR correctors and potentiators show comparable effects to existing ones in vitro, and their combination can enhance the improvement of CFTR function with terminal PTC mutations.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Laure Bidou, Olivier Bugaud, Goulven Merer, Matthieu Coupet, Isabelle Hatin, Egor Chirkin, Sabrina Karri, Stephane Demais, Pauline Francois, Jean-Christophe Cintrat, Olivier Namy
Summary: In this study, a new drug was developed and evaluated for its clinical potential in treating genetic diseases caused by premature termination codons (PTCs). The drug, TLN468, was found to be more effective than the currently used gentamicin and acted on a broader range of sequences without affecting normal stop codon readthrough.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Maciej Dabrowski, Zuzanna Bukowy-Bieryllo, Claire L. Jackson, Ewa Zietkiewicz
Summary: The study identified several non-aminoglycoside compounds with potential to induce PTC-readthrough, which demonstrated minimal negative impact on cell viability and function compared to aminoglycosides, although with lower efficiency.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Roland N. Wagner, Michael Wiessner, Andreas Friedrich, Johanna Zandanell, Hannelore Breitenbach-Koller, Johann W. Bauer
Summary: This review summarizes the current understanding of translation termination and highlights newly discovered pathways that influence its fidelity. It also describes the mechanisms involved in the recognition and readthrough of premature termination codons (PTCs) and reports on compounds that induce PTC readthrough. The ongoing attempts of personalized nonsense suppression therapy in different disease contexts are also reviewed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Daniel R. McHugh, Calvin U. Cotton, Craig A. Hodges
Summary: This study demonstrated synergy between NMD inhibitors and readthrough agents in increasing functional protein quantity following readthrough, suggesting a potential therapeutic option for treating nonsense mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Jyoti Sharma, Ming Du, Eric Wong, Venkateshwar Mutyam, Yao Li, Jianguo Chen, Jamie Wangen, Kari Thrasher, Lianwu Fu, Ning Peng, Liping Tang, Kaimao Liu, Bini Mathew, Robert J. Bostwick, Corinne E. Augelli-Szafran, Hermann Bihler, Feng Liang, Jerome Mahiou, Josef Saltz, Andras Rab, Jeong Hong, Eric J. Sorscher, Eric M. Mendenhall, Candice J. Coppola, Kim M. Keeling, Rachel Green, Martin Mense, Mark J. Suto, Steven M. Rowe, David M. Bedwell
Summary: In this study, compounds with readthrough activity were identified and shown to reduce premature termination associated with cystic fibrosis by lowering eRF1 levels. These compounds, including SRI-41315 and SRI-37240, have potential as promising treatment strategies for diseases caused by PTCs.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Suji Kim, No-Joon Song, Seo-Hyuk Chang, Gahee Bahn, Yuri Choi, Dong-Kwon Rhea, Ui Jeong Yun, Jinhee Choi, Jeon Lee, Jae Hyuk Yoo, Donghan Shin, Ki-Moon Park, Hee Kang, Sukchan Lee, Jin-Mo Ku, Yoon Shin Cho, Kye Won Park
BIOMOLECULES & THERAPEUTICS
(2019)
Article
Oncology
Lingfan Xu, Enze Ma, Tao Zeng, Ruya Zhao, Yulei Tao, Xufeng Chen, Jeff Groth, Chaozhao Liang, Hailiang Hu, Jiaoti Huang
ENDOCRINE-RELATED CANCER
(2019)
Article
Biochemistry & Molecular Biology
Yu Yin, Lingfan Xu, Yan Chang, Tao Zeng, Xufeng Chen, Aifeng Wang, Jeff Groth, Wen-Chi Foo, Chaozhao Liang, Hailiang Hu, Jiaoti Huang
Correction
Biochemistry & Molecular Biology
Yu Yin, Lingfan Xu, Yan Chang, Tao Zeng, Xufeng Chen, Aifen Wang, Jeff Groth, Wen-Chi Foo, Chaozhao Liang, Hailiang Hu, Jiaoti Huang
Article
Chemistry, Medicinal
Hoon Choi, Wheesahng Yun, Jung-hun Lee, Seoul Jang, Sang Won Park, Dong Hwan Kim, Kyoung Pyo Seon, Jung-mi Hyun, Kwiwan Jeong, Jin-mo Ku, Tae-gyu Nam
MEDICINAL CHEMISTRY RESEARCH
(2019)
Article
Chemistry, Organic
Kunyoung Kim, Sang Hoon Han, Daeun Jeoung, Prithwish Ghosh, Saegun Kim, Seung Jun Kim, Jin-Mo Ku, Neeraj Kumar Mishra, In Su Kim
JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Cell Biology
Yanjing Li, Yiping He, William Butler, Lingfan Xu, Yan Chang, Kefeng Lei, Hong Zhang, Yinglu Zhou, Allen C. Gao, Qingfu Zhang, Daniel G. Taylor, Donghui Cheng, Suzette Farber-Katz, Rachid Karam, Tyler Landrith, Bing Li, Sitao Wu, Vickie Hsuan, Qing Yang, Hailiang Hu, Xufeng Chen, Melissa Flowers, Shannon J. McCall, John K. Lee, Bryan A. Smith, Jung Wook Park, Andrew S. Goldstein, Owen N. Witte, Qianben Wang, Matthew B. Rettig, Andrew J. Armstrong, Qing Cheng, Jiaoti Huang
SCIENCE TRANSLATIONAL MEDICINE
(2019)
Review
Chemistry, Medicinal
Cheng Fang, Lan Wu, Cong Zhu, Wen-Zhong Xie, Hailiang Hu, Xian-Tao Zeng
Summary: Human microbiome research has shown the critical role of oral microbiome in health and disease, with dysbiosis being a contributory cause for diseases in multiple body systems, including a possible link between periodontal disease and prostatic disease. Research is progressing towards oral microbiome-based diagnosis and therapy for potential drug targets in systemic diseases.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Oncology
Yi Sun, Jun Jing, Huan Xu, Lingfan Xu, Hailiang Hu, Cai Tang, Shengzhuo Liu, Qiang Wei, Ruiqi Duan, Ju Guo, Lu Yang
Summary: The study showed that N-cadherin upregulated PD-L1 and IDO-1 expression through interferon-gamma signaling, promoting eTreg cell generation. ADH-1 effectively reduced immunosuppression and enhanced TIL-related therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
A. Jun, Baotong Zhang, Zhiqian Zhang, Hailiang Hu, Jin-Tang Dong
Summary: Molecular signatures predictive of recurrence-free survival and castration resistance in prostate cancer are crucial for treatment decisions, but current signatures have limited robustness. By analyzing 287 differentially expressed genes, a 6-gene signature called CRPC-derived prognosis signature (CRPCPS) was identified to predict recurrence-free survival and distinguish between castration-resistant and hormone-sensitive prostate cancer. The robustness of this signature was demonstrated in multiple cohorts, showing its potential clinical utility.
Article
Multidisciplinary Sciences
Lingfan Xu, Yu Yin, Yanjing Li, Xufeng Chen, Yan Chang, Hong Zhang, Juan Liu, James Beasley, Patricia McCaw, Haoyue Zhang, Sarah Young, Jeff Groth, Qianben Wang, Jason W. Locasale, Xia Gao, Dean G. Tang, Xuesen Dong, Yiping He, Daniel George, Hailiang Hu, Jiaoti Huang
Summary: This study identifies a metabolic mechanism in prostate cancer where a switch in glutaminase isoforms contributes to therapeutic resistance and disease progression. The expression of GAC leads to increased glutamine utilization and aggressive behavior of tumor cells in the absence of androgen, ultimately impacting treatment outcomes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Huan Xu, Sangsang Li, Yi Sun, Lingfan Xu, Xin Hong, Zhong Wang, Hailiang Hu
Summary: This study reveals the impact of long-chain polyunsaturated fatty acid ELOVL5 on enzalutamide resistance and neuroendocrine differentiation in prostate cancer, providing a potential therapeutic target for treating enzalutamide-resistant NE-like prostate cancer.
Review
Biochemistry & Molecular Biology
Haozhe Zhang, Yi Zhou, Zengzhen Xing, Rajiv Kumar Sah, Junqi Hu, Hailiang Hu
Summary: This review discusses the close relationship between the evolution of prostate cancer and androgen levels and the status of the androgen receptor. It also explores how alterations in androgen metabolism contribute to the resistance to anti-androgen therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Susoma Jannat, Anand Balupuri, Md Yousof Ali, Seong Su Hong, Chun Whan Choi, Yun-Hyeok Choi, Jin-Mo Ku, Woo Jung Kim, Jae Yoon Leem, Ju Eun Kim, Abinash Chandra Shrestha, Ha Neul Ham, Kee-Ho Lee, Dong Min Kim, Nam Sook Kang, Gil Hong Park
EXPERIMENTAL AND MOLECULAR MEDICINE
(2019)
Review
Urology & Nephrology
Lingfan Xu, Junyi Chen, Weipeng Liu, Chaozhao Liang, Hailiang Hu, Jiaoti Huang
ASIAN JOURNAL OF UROLOGY
(2019)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
