Article
Biochemistry & Molecular Biology
Shahid Parwez, Pinaki Parsad Mahapatra, Shakil Ahmed, Mohammad Imran Siddiqi
Summary: A deep neural network-based workflow was proposed for the virtual screening of compounds targeting TACE proteins. Three compounds showed significant inhibition and stable interaction potential against TACE protein, making them potential candidates for further development as novel inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Jinbao Xiang, Yuji Wang, Wanhe Wang, Jianxin Yu, Lianyou Zheng, Yuan Hong, Lingling Shi, Chunling Zhang, Na Chen, Jia Xu, Xuelian Gong, Zhuoqi Zhang, Hongming Cui, Qian Zhou, Dapeng Zhang, Yanjun Liu, Ying Ke, Jingkang Shen, Guangxin Xia, Xu Bai
Summary: We report the design, synthesis, and structure-activity relationships (SARs) of a series of novel quinazoline derivatives as JAK inhibitors. Among these inhibitors, compound 11n showed high potency against JAKs (JAK1/JAK2/JAK3/TYK2, IC50 = 0.40, 0.83, 2.10, 1.95 nM), desirable metabolic characters, and excellent pharmacokinetic properties. In collagen-induced arthritis (CIA) models, compound 11n exhibited significant reduction in joint swelling with good safety, which could be served as a potential therapeutic candidate for the treatment of inflammatory diseases.
BIOORGANIC CHEMISTRY
(2023)
Article
Rheumatology
Benjamin Clarke, Mark Yates, Maryam Adas, Katie Bechman, James Galloway
Summary: As efficacy and safety data emerge, differences between JAK inhibitor subclasses are becoming evident. It is too early to conclude on distinct safety profiles between JAK1 selective agents and other JAK inhibitors, with further research needed for support. Monitoring infection risk, laboratory abnormalities, and herpes zoster reactivation are important considerations when using JAK inhibitors.
Article
Pharmacology & Pharmacy
Kai Huang, Ying Ding, Linling Que, Nannan Chu, Yunfei Shi, Zhenzhong Qian, Wei Qin, Yuanxin Chen, Xianghong Gu, Jiakun Wang, Zhiwei Zhang, Jianguo Xu, Qing He
Summary: This study aimed to investigate the safety, tolerability, and pharmacokinetics of WXFL10203614 in healthy Chinese subjects. A total of 592 subjects were enrolled, and results showed good safety and tolerability of WXFL10203614 in all dose levels, with dose-related changes in pharmacokinetic parameters. The findings support further clinical development of WXFL10203614 in patients with rheumatoid arthritis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Salvatore D'Angelo, Enrico Tirri, Angela Maria Giardino, Marco Mattucci-Cerinic, Lorenzo Dagna, Leonardo Santo, Francesco Ciccia, Bruno Frediani, Marcello Govoni, Francesca Bobbio Pallavicini, Rosa Daniela Grembiale, Andrea Delle Sedie, Rita Mule, Francesco Paolo Cantatore, Rosario Foti, Elisa Gremese, Paola Conigliaro, Fausto Salaffi, Ombretta Viapiana, Alberto Cauli, Roberto Giacomelli, Luisa Arcarese, Giuliana Guggino, Romualdo Russo, Amy Puenpatom, Domenico Capocotta, Francesca Nacci, Maria Grazia Anelli, Valentina Picerno, Corrado Binetti, Florenzo Iannone
Summary: This prospective observational study collected data from rheumatology clinics in Italy and found that golimumab (GLM) as a second anti-TNF drug is effective in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). GLM improved disease activity and quality of life in these patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Rheumatology
Mark C. Genovese, Alberto Spindler, Akira Sagawa, Won Park, Anna Dudek, Alan Kivitz, Jeannie Chao, Lai Shan Melanie Chan, Jennifer Witcher, William Barchuk, Ajay Nirula
Summary: This study evaluated the efficacy and safety of poseltinib in treating RA patients, but was terminated after interim data showed low likelihood of benefit.
JOURNAL OF RHEUMATOLOGY
(2021)
Article
Medicine, General & Internal
Borja Hernandez-Breijo, Claudia M. Brenis, Chamaida Plasencia-Rodriguez, Ana Martinez-Feito, Marta Novella-Navarro, Dora Pascual-Salcedo, Alejandro Balsa
Summary: The study found that TNFi survival did not depend on seropositivity status, but seropositive patients who received concomitant MTX had significantly longer median survival time. Additionally, the co-administration of prednisone in seropositive patients receiving TNFi was highly associated with TNFi discontinuation.
FRONTIERS IN MEDICINE
(2021)
Article
Multidisciplinary Sciences
Yi-Shu Huang, Wen-Yi Tseng, Felix I. L. Clanchy, Louise M. Topping, Joy Ogbechi, Kay McNamee, Dany Perocheau, Nien-Yi Chiang, Peter Ericsson, Anette Sundstedt, Zhong-Tian Xue, Leif G. Salford, Hans-Olov Sjogren, Trevor W. Stone, Hsi-Hsien Lin, Shue-Fen Luo, Richard O. Williams
Summary: The study found that decitabine can promote the generation of regulatory T cells and has the potential to treat rheumatoid arthritis. It alleviates inflammation by inducing the expansion of induced regulatory T cells and selectively inducing apoptosis of Th1 and Th17 cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Izzuddin Ahmad Nadzirin, Adam Leow Thean Chor, Abu Bakar Salleh, Mohd Basyaruddin Abdul Rahman, Bimo A. Tejo
Summary: Rheumatoid arthritis is an inflammatory autoimmune disease affecting about 0.24% of the world population, and PAD4 is believed to be responsible for its occurrence. Peptide inhibitors designed to target PAD4 can reduce its activity, with P2 (Cav) showing potential as an inhibitor against PAD4 based on experimental data.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2021)
Article
Immunology
Xiaojuan Zhang, Xin Xu, Jia Chen, Guan Wang, Qiang Li, Min Li, Jianzhong Lu
Summary: HHT-9041P1, a selective JAK1 inhibitor, has shown high selectivity and preclinical efficacy in vitro and in vivo experiments, making it a potential candidate for the treatment of RA.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Rheumatology
John Fitton, Andrew R. Melville, Paul Emery, Jacqueline L. Nam, Maya H. Buch
Summary: The study evaluated the real-world efficacy of approved JAK inhibitors in RA patients, including those refractory to previous biologic drugs. The results showed significant efficacy of JAK inhibition in some patients, with no unexpected safety events.
Article
Rheumatology
Roswitha Dietzel, Sabine Wiegmann, Diana Borucki, Christian Detzer, Kim Nikola Zeiner, Desiree Schaumburg, Bjoern Buehring, Frank Buttgereit, Gabriele Armbrecht
Summary: In patients with rheumatoid arthritis (RA), chronic inflammation can lead to muscle depletion. The study found that sarcopenia is more common in RA patients and is associated with factors such as body weight, BMI, inflammation markers, and disease duration.
Article
Medicine, General & Internal
Ewa Zelnio, Mihra Taljanovic, Malgorzata Manczak, Iwona Sudol-Szopinska
Summary: The hand and wrist are frequently involved in rheumatic diseases, and this study aimed to identify the distinguishing radiographic characteristics of psoriatic arthritis (PsA), seropositive rheumatoid arthritis (RA), and seronegative RA, especially in the early stages. The analysis of radiographic hand findings on 180 seropositive RA patients, 154 PsA patients, and 36 seronegative RA patients revealed that symmetric distribution of lesions was more suggestive of seropositive or seronegative RA, while lesions affecting PIP joints, wrist, or styloid process of the radius were more common in patients with seropositive RA. PsA was more likely to be suggested by DIP joints' involvement and proliferative bone changes. Furthermore, there were differences in the types of bone lesions and their distribution between seropositive RA, seronegative RA, and PsA, with ulnar styloid involvement more commonly seen in seronegative RA patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Rheumatology
Farzin Khosrow-Khavar, Seoyoung C. Kim, Hemin Lee, Su Been Lee, Rishi J. Desai
Summary: The study did not find evidence of increased cardiovascular risk with tofacitinib in patients with RA in a real-world setting. However, tofacitinib was associated with an increased risk of cardiovascular outcomes, although statistically non-significant, in patients with RA with cardiovascular risk factors.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Medicine, General & Internal
Jumpei Temmoku, Masayuki Miyata, Eiji Suzuki, Yuya Sumichika, Kenji Saito, Shuhei Yoshida, Haruki Matsumoto, Yuya Fujita, Naoki Matsuoka, Tomoyuki Asano, Shuzo Sato, Hiroshi Watanabe, Kiyoshi Migita
Summary: This study found that drug-induced lymphocytopenia is associated with reduced drug retention rates of JAK inhibitors (tofacitinib or baricitinib) in rheumatoid arthritis (RA) patients. A quarter of RA patients treated with JAK inhibitors showed lymphocytopenia, which was associated with lower drug retention rates of tofacitinib but not baricitinib. Pre-treatment absolute lymphocyte counts did not affect the drug retention rates of JAK inhibitors in patients with RA.
JOURNAL OF CLINICAL MEDICINE
(2023)
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)