Article
Chemistry, Medicinal
Martina De Pascale, Lukas Bissegger, Chiara Tarantelli, Florent Beaufils, Alessandro Prescimone, Hayget Mohamed Seid Hedad, Omar Kayali, Clara Orbegozo, Luka Raguz, Thorsten Schaefer, Paul Hebeisen, Francesco Bertoni, Matthias P. Wymann, Chiara Borsari
Summary: The study identifies DHP and THP as isosteres of the morpholine moiety that can be used to generate novel TORKi drugs. Compound 11b is selected as a potent and selective mTOR kinase inhibitor with good metabolic stability and oral bioavailability. In cell experiments, compound 11b demonstrates dose-dependent anti-proliferative activity in splenic marginal zone lymphoma cell lines and synergistic effects with venetoclax.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Neurosciences
Henry Querfurth, Han-Kyu Lee
Summary: mTOR is involved in regulating energy metabolism, neuronal growth, insulin signaling, and autophagy, playing both beneficial and pathogenic roles in neurodegenerative diseases. Balanced actions of mTOR complexes may have implications for Alzheimer's disease, Parkinson's disease, Huntington's disease, Frontotemporal dementia, and Amyotrophic Lateral Sclerosis. Beyond rapamycin, rapalogs with improved tolerability and delivery modes hold promise in treating age-related conditions.
MOLECULAR NEURODEGENERATION
(2021)
Article
Medicine, Research & Experimental
Mohamed El-Tanani, Hamdi Nsairat, Alaa A. Aljabali, Angel Serrano-Aroca, Vijay Mishra, Yachana Mishra, Gowhar A. Naikoo, Walhan Alshaer, Murtaza M. Tambuwala
Summary: The mammalian target of rapamycin (mTOR), a signalling system, is necessary for various cell proliferation activities. It recognizes PI3KAKT stress signals as a serine-threonine kinase. The abnormal regulation of mTOR pathway has been proven to be crucial in cancer growth and advancement. This review primarily discusses the normal functions of mTOR as well as its abnormal roles in cancer development.
Article
Chemistry, Medicinal
Bernard Barlaam, Chris De Savi, Allan Dishington, Lisa Drew, Andrew D. Ferguson, Douglas Ferguson, Chungang Gu, Sudhir Hande, Lorraine Hassall, Janet Hawkins, Alexander W. Hird, Jane Holmes, Michelle L. Lamb, Andrew S. Lister, Thomas M. McGuire, Jane E. Moore, Nichole O'Connell, Anil Patel, Kurt G. Pike, Ujjal Sarkar, Wenlin Shao, Darren Stead, Jeffrey G. Varnes, Melissa M. Vasbinder, Lei Wang, Liangwei Wu, Lin Xue, Bin Yang, Tieguang Yao
Summary: The discovery of azaindoles 38 and 39 as highly potent and selective CDK9 inhibitors suitable for intravenous administration, with the potential to achieve transient inhibition of CDK9 in vivo, represents a significant advancement in the development of treatment for hematological malignancies. Further optimization focusing on physicochemical and pharmacokinetic properties played a crucial role in the development of these compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Patrik Oleksak, Eugenie Nepovimova, Zofia Chrienova, Kamil Musilek, Jiri Patocka, Kamil Kuca
Summary: Mechanistic target of rapamycin (mTOR) is a protein kinase that regulates cell functions. Dysregulation of mTOR activity is associated with various pathological conditions. Inhibition of overactivated mTOR is a rational approach for treating human diseases. Rapamycin is a natural inhibitor of mTOR with antitumor and immunosuppressive activity. Different generations of mTOR inhibitors have been developed, including rapalogs, mTOR kinase inhibitors, and dual PI3K/mTOR inhibitors. Novel inhibitors are still being developed to better understand the role of mTOR in signaling pathways and human diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Ophthalmology
Nozomi Igarashi, Megumi Honjo, Makoto Aihara
Summary: Glaucoma, the second leading cause of blindness worldwide, is often treated with trabeculectomy, but this surgery can lead to excessive scarring and tissue fibrosis. Studies have shown that mTOR inhibitors may offer a new treatment modality for reducing fibrotic response in human conjunctival fibroblasts and improving bleb scarring after filtration surgery.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Alaa Abou Daher, Sahar Alkhansa, William S. Azar, Rim Rafeh, Hilda E. Ghadieh, Assaad A. Eid
Summary: Understanding the mechanisms behind diabetic nephropathy (DN) is crucial for developing effective treatments. The mTOR pathway has been identified as a key player in diabetes-induced kidney injury, through its involvement in insulin resistance, oxidative stress, and autophagy regulation.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Medicine, Research & Experimental
Pengxing He, Jing Jing, Linna Du, Xuyang Zhang, Yufei Ren, Han Yang, Bin Yu, Hongmin Liu
Summary: YS-363 is a novel EGFR inhibitor that demonstrates potent reversible inhibition and excellent activities against cell proliferation, migration, cell cycle and apoptosis. It is a promising selective inhibitor that can potentially be developed as a more effective anti-lung cancer agent targeting EGFR.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Immunology
Preeti Vyas, Rajkumar Tulsawani, Divya Vohora
Summary: Recent findings show that neuroinflammation is closely related to seizures, and the PI3K/Akt/mTOR pathway is speculated to be a potential target for treating neuroinflammation-mediated seizures and neurodegeneration. In a study on mice, PI3K inhibitors buparlisib and dactolisib were found to be effective in prolonging seizure latency and reducing neuronal loss, while rapamycin showed some resistance. The study suggests that targeting the PI3K pathway may offer new approaches for seizure therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ying-Yue Yang, Wan-Li Wang, Xia-Tong Hu, Xin Chen, Yang Ni, Yan-Hua Lei, Qi-Yuan Qiu, Long-Yue Tao, Tian -Wen Luo, Ning-Yu Wang
Summary: The mammalian target of rapamycin (mTOR) has been proven to be an effective target for cancer therapy. Rapalogs and mTOR kinase inhibitors (TORKi) have been developed and clinically validated in several types of malignancies, with TORKi showing better antitumor activity by inhibiting both mTORC1 and mTORC2. However, the clinical development of current TORKi candidates has been relatively slow, and there is a need to develop more TORKi with novel scaffold to expand the current pipelines.
BIOORGANIC CHEMISTRY
(2023)
Article
Oncology
Fan Lin, Yunqi Liu, Lili Tang, Xiaohui Xu, Xueli Zhang, Yifan Song, Bicheng Chen, Yeping Ren, Xiangdong Yang
Summary: The study demonstrated that rapamycin protects against aristolochic acid-induced nephropathy by activating the mTOR-autophagy axis. This finding provides evidence for rapamycin as a promising pharmacological target for the treatment of aristolochic acid nephropathy.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Biotechnology & Applied Microbiology
Andrea Perez-Iturralde, Beatriz Carte, Rafael Aldabe
Summary: The study found that mTOR inhibitors have complex effects on AAV hepatic transduction efficiency, with rapamycin enhancing AAV transduction while RapaLink-1 and MLN0128 do not. This indicates that mTOR inhibition is not a straightforward strategy for improving AAV transduction, and more research is needed to elucidate the mechanisms involved in their effects.
HUMAN GENE THERAPY
(2021)
Article
Chemistry, Medicinal
Peng Zhao, Linghang Zhuang, Xiangzhu Wang, Song Huang, Heping Wu, Yu Zhou, Yuna Yan, Fan Zhang, Ru Shen, Jing Li, Suxing Liu, Rumin Zhang, Ping Dong, Yuchang Mao, Yuanmin Fan, Chunyong He, Jiakang Sun, Lei Zhang, Qiyue Hu, Hong Wan, Jun Feng, Chang Bai, Feng He, Weikang Tao
Summary: A molecule called SHR902275 (or molecule 33) has been discovered with significantly improved potency and solubility, which shows potential for targeting cancers with mutant RAS and wild type RAF activity. In vivo experiments have demonstrated dose dependent efficacy of molecule 33.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yin Sun, Yanli Xue, Pengkun Sun, Shuyi Mu, Hongbing Liu, Yu Sun, Lin Wang, Jingkai Wang, Tianxiao Wu, Wenbo Yin, Qiaohua Qin, Yixiang Sun, Nian Liu, Hanxun Wang, Huali Yang, Dongmei Zhao, Maosheng Cheng
Summary: A study discovered SP27 as the first selective PLK4 PROTAC degrader, which effectively degrades PLK4 and exhibits more potent inhibition of cell growth in TRIM37-amplified breast cancer. This finding is of great significance for the treatment of this cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Douglas R. Wassarman, Kondalarao Bankapalli, Leo J. Pallanck, Kevan M. Shokat
Summary: Mammalian target of rapamycin (mTOR) is a crucial factor in cell growth and metabolism, and its signaling in different tissues affects whole-organism processes. Researchers have developed selecTOR, a chemical-genetic system that restricts the activity of rapamycin analog in specific cell populations, achieving selective mTOR inhibition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Medicinal
Li-Chuan Liu, Xin-Yu Li, Yu Qin, Mei-Han Liu, Xiang Xing
CHEMISTRY OF NATURAL COMPOUNDS
(2022)
Article
Multidisciplinary Sciences
Kun An, Wenpeng Ma, Li-Chuan Liu, Tao He, Guiyu Guan, Qing-Wei Zhang, Wei He
Summary: This study presents a method for enantioselective intermolecular C-H bond silylation, leading to the construction of a wide array of acyclic stereogenic Si-H compounds under simple and mild reaction conditions. The results highlight opportunities in converting simple arenes into value-added stereogenic silicon compounds.
NATURE COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Chun-Ting Liu, I-Ling Hung, Chung Y. Hsu, Kai-Chieh Hu, Yung-Hsiang Chen, Ming-Yen Tsai
Summary: This study found that Chinese herbal medicine (CHM) use can reduce the risk of heart failure in hypertensive patients. Long-term use of CHM has a significant effect on reducing risk, and some commonly used CHM formulas and single herbs are significantly associated with lower risk of heart failure.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Mechanics
Yu-fang Zheng, De-yong Qu, Li-chuan Liu, Chang-ping Chen
Summary: In this study, a nonlinear bending model of the nonlocal three-layer magneto-electro-elastic (MEE) laminated nanobeam resting on elastic foundation is established using Reddy's third-order shear deformation theory (RTSDT) and nonlocal elasticity theory. The model considers the geometrically nonlinear equations proposed by von Karman and also takes into account the effects of electric and magnetic potentials in the laminated nanobeam through Maxwell's magnetic-electro equations and boundary conditions. The governing equations are re-expressed in a dimensionless form and simplified using the Galerkin method. The study explores the effects of foundation parameters, nonlocal parameter, stacking sequence, external electric voltage and external magnetic potential on the bending behaviors of MEE laminated nanobeams.
INTERNATIONAL JOURNAL OF NON-LINEAR MECHANICS
(2023)
Article
Plant Sciences
Yu-Hung Lai, Wei-Lun Liu, Tsung-Ying Lee, Chung-Wen Kuo, Yu-Ru Liu, Chi-Yuan Huang, Yung-Hsiang Chen, I-Ling Chen, Szu-Hui Wu, Shu-Chi Wang, Po-Yen Lee, Ching-Chih Liu, Jung Lo, Yo-Chen Chang, Hsuan-Fu Kuo, Chong-Chao Hsieh, Chia-Yang Li, Po-Len Liu
Summary: This study aimed to investigate the treatment of retinoblastoma caused by early embryonic development. The results showed that Magnolol could inhibit the development of retinoblastoma by regulating EMT, suppressing tumor growth and metastasis.
Article
Engineering, Multidisciplinary
Yu-fang Zheng, Li-Chuan Liu, De-yong Qu, Chang-ping Chen
Summary: This article presents the nonlinear postbuckling behavior of magneto-electro-thermo-elastic (METE) laminated microbeams. Based on the modified couple stress theory and Reddy's three-order shear deformation theory, along with the von Karman geometric nonlinearity, the nonlinear static model of METE laminated microbeam is established. The nonlinear governing equations and boundary conditions are derived using the principle of virtual work principle. An analytical method is then used to describe the nonlinear postbuckling behavior of METE laminated microbeam with simple supported and clamped boundary conditions. Numerical examples are provided to reveal the effects of various parameters on the critical buckling load and postbuckling response, as well as the distribution of magneto-electric potential through the thickness direction of the microbeam with different lay-up modes.
APPLIED MATHEMATICAL MODELLING
(2023)
Article
Biology
I. -Fan Liu, Tzu-Chieh Lin, Shu-Chi Wang, Chia-Hung Yen, Chia-Yang Li, Hsuan-Fu Kuo, Chong-Chao Hsieh, Chia-Yuan Chang, Chuang-Rung Chang, Yung-Hsiang Chen, Yu-Ru Liu, Tsung-Ying Lee, Chi-Yuan Huang, Chih-Hsin Hsu, Shing-Jong Lin, Po-Len Liu
Summary: Long-term consumption of excessive fat and sucrose diet can lead to metabolic syndrome and cardiovascular disease. The study found that CAV-1 and caveolae proteins are related to abnormal lipid accumulation in the endothelium and myocardium, as well as dysfunction in microvascular endothelial cells and mitochondrial remodeling.
Article
Oncology
Daniel Winardi, Chieh-Hsin Wu, Jen-Huai Chiang, Yung-Hsiang Chen, Ching-Liang Hsieh, Juan-Cheng Yang, Yang-Chang Wu
Summary: In this retrospective cohort study, the influence of San-Huang-Xie-Xin-Tang (SHXXT) and its constituents on the mortality rate of breast cancer patients was explored. The study confirmed that SHXXT and its constituents are a useful alternative therapy in decreasing breast cancer mortality rate. The anti-tumor effect is more pronounced with increasing cumulative days of use and annual average dose.
Article
Medicine, General & Internal
Jia-Jyun Jhang, Szu-Ju Chen, Chi-Ping Huang, Huey-Yi Chen, Wei-Ching Lin, Yung-Hsiang Chen, Wen-Chi Chen
Summary: This case report presents a 28-year-old male patient with spontaneous intratesticular hematoma. Initial suspicion of testicular malignancy was ruled out and a hematoma was diagnosed, possibly related to long-term use of sulfasalazine.
Review
Biochemistry & Molecular Biology
Chien-Zhi Lai, Szu-Ju Chen, Chi-Ping Huang, Huey-Yi Chen, Ming-Yen Tsai, Po-Len Liu, Yung-Hsiang Chen, Wen-Chi Chen
Summary: Varicocele is a common urological disorder with a prevalence rate of 8% to 15% in healthy men. However, the incidence is higher in male patients with infertility, with up to 35% to 80% of cases occurring in this population. Clinical manifestations of varicocele include an asymptomatic mass, chronic scrotal pain, and infertility. Postoperative scrotal pain may persist due to varicocele recurrence, hydrocele, neuralgia, referred pain, ureteral lesions, or nutcracker syndrome. Clinicians should consider these conditions as potential causes and take measures to address them in order to optimize surgical outcomes.
Article
Health Care Sciences & Services
Yi-Huei Chang, Szu-Ying Pan, Chia-Yu Lin, Chi-Ping Huang, Chi-Jung Chung, Yung-Hsiang Chen, Wen-Chi Chen
Summary: Prostate abscess (PA) is a potentially life-threatening condition that requires prompt treatment. However, the declining incidence of PA in developing countries and high-risk patients can hinder early diagnosis. This study aimed to review the etiology, pathophysiology, diagnosis, and treatment options for PA, as well as analyze the characteristics and clinical course of patients. The findings can guide the development of a personalized treatment strategy for patients with PA.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Chemistry, Medicinal
Shen-Wei Hou, Szu-Ju Chen, Jing-Dung Shen, Huey-Yi Chen, Shih-Jing Wang, Chia-Han Wang, Kee-Ming Man, Po-Len Liu, Ming-Yen Tsai, Yung-Hsiang Chen, Wen-Chi Chen
Summary: This study aimed to explore the therapeutic effect of emodin, a Chinese herbal extract, in a rat model of hyperuricemia and gout. The results demonstrated that emodin reduced serum uric acid levels and achieved effective treatment of hyperuricemia and gout by increasing urinary excretion.
Article
Biology
Po-Chih Lai, Chia-Ming Yen, Ming-Chia Lin, Yung-Hsiang Chen, Hsien-Yin Liao, Yu-Wei Huang, Yi-Wen Lin
Summary: This study found that the activation of Toll-like receptor 4 (TLR4) pathway is involved in fibromyalgia (FM) pain. Electroacupuncture (EA) can alleviate pain symptoms in FM patients by inhibiting inflammatory response, providing new possibilities for FM treatment.
Article
Medicine, General & Internal
Szu-Ying Pan, Chien-Zhi Lai, Wen-Chi Chen, Yung-Hsiang Chen, Che-Hung Lin, Han Chang, Chi-Ping Huang, Ching-Chung Yeh
Summary: Chondrosarcoma of the upper urinary tract is a rare condition with clinical manifestations similar to other urinary tract diseases. Surgical removal of the tumor is the primary treatment, with radiation or chemotherapy used for advanced cases. However, due to limited patient numbers, there are no established guidelines for chemotherapy and the outcomes of treatment are unclear.
MEDICINA-LITHUANIA
(2023)
Article
Medicine, General & Internal
Szu-Ying Pan, Chi-Ping Huang, Wen-Chi Chen, Yung-Hsiang Chen, Eric Chieh-Lung Chou
Summary: Endoscopic combined intrarenal surgery (ECIRS) is a new operative technique that integrates the advantages of PCNL and RIRS for the treatment of staghorn stones. We performed RIRS followed by PCNL in a 72-year-old female patient, which provided a more convenient and effective approach with high stone reduction efficiency and no complications.
MEDICINA-LITHUANIA
(2023)