Tanja Hann、Harim Jang、Yu-Chieh Sung、Chia-Lun Guh、Nicholas M Hiers、Lucille H Tsao、Michelle Luo、Anna Marie Pyle
作者机构
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.
Department of Chemistry, Yale University, New Haven, CT, USA.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Department of Chemistry, Yale University, New Haven, CT, USA. Electronic address: anna.pyle@yale.edu.
High-throughput protein interactome identifies LSD1 as a regulator of SARS-CoV-2 production through lysine demethylation of viral nucleocapsid protein.
State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; School of Life Sciences, Henan University, Kaifeng, China.
State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, Shenzhen, China; State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. Electronic address: zhangxe@ibp.ac.cn.
State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, Shenzhen, China. Electronic address: mh.chen1@siat.ac.cn.
Remibrutinib是一种高选择性、强效、共价、可穿透中枢神经系统的口服BTK抑制剂。REMODEL-1和REMODEL-2为两项相同的随机、双盲、双模拟、活性对照、平行组、事件驱动Ⅲ期试验，在46个国家407个中心开展，纳入18-55岁、EDSS评分0-5.5、有近期疾病活动证据的复发型多发性硬化患者，按1:1随机接受口服remibrutinib 100 mg每日两次或特立氟胺14 mg每日一次，主要终点为年化复发率（ARR）。2021年12月13日至2025年12月30日筛查2632例，随机分配2007例；REMODEL-1纳入1000例，REMODEL-2纳入1007例。remibrutinib组ARR显著低于特立氟胺组：REMODEL-1为0.073 vs 0.112（RR 0.648，95%CI 0.453-0.927；p=0.018），REMODEL-2为0.080 vs 0.116（RR 0.688，95%CI 0.487-0.972；p=0.034）。最常见不良事件为上呼吸道感染、鼻咽炎、腹泻和脱发；导致停药的不良事件remibrutinib组较少（3.1% vs 5.8%），安全性与其他适应症一致，无肝脏安全性担忧。研究表明remibrutinib优于特立氟胺且安全性良好，支持其作为复发型多发性硬化潜在新型口服治疗选择。
Department of Neurology and Neurophysiology, University of Freiburg, Freiburg, Germany; Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia. Electronic address: heinz.wiendl@uniklinik-freiburg.de.
Department of Neurology, Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, USA.
Turku PET Centre, Clinical Neurosciences and InFLAMES Research Flagship, University of Turku, Turku, Finland; Neurocenter, Turku University Hospital, Turku, Finland.
Brigham Multiple Sclerosis Center and Division of Neuroimmunology, Mass General Brigham, Boston, MA, USA.
Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
Joi Life Wellness Neurology Clinic, Smyrna, GA, USA.
Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland.
MedPolonia, Outpatient MS Clinic, Poznań, Poland; Department of Medical Education and Communication, Poznan University of Medical Sciences, Poznań, Poland.
Novartis Pharma, Basel, Switzerland.
Novartis Ireland, Dublin, Ireland.
Novartis Institutes for Biomedical Research, Shanghai, China.
Novartis Pharmaceuticals Corporation, Cambridge, MA, USA.
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Barcelona, Spain.
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