Kushnir Alexander, Marks Andrew R
Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, 1400 Pelham ParkwaySouth, New York, NY 10461, USA.
Recent Pat Biotechnol. 2012 Dec;6(3):157-66. doi: 10.2174/1872208311206030157.
Research over the past two decades has implicated dysfunction of the ryanodine receptor (RyR), a Ca(2+) release channel on the sarcoplasmic reticulum (SR) required for excitation-contraction (EC) coupling, in the pathogenesis of cardiac and skeletal myopathies. These discoveries have led to the development of novel drugs, screening tools, and research methods. The patents associated with these advances tell the story of the initial discovery of RyRs as a target for plant alkaloids, to their central role in cardiac and skeletal muscle excitation-contraction coupling, and ongoing clinical trials with a novel class of drugs called RycalsTM that inhibit pathological intracellular Ca(2+) leak. Additionally, these patents highlight questions, controversies, and future directions of the RyR field.
过去二十年的研究表明,兰尼碱受体(RyR)功能障碍与心肌和骨骼肌疾病的发病机制有关。RyR是肌浆网(SR)上的一种钙释放通道,是兴奋-收缩(EC)偶联所必需的。这些发现推动了新型药物、筛选工具和研究方法的发展。与这些进展相关的专利讲述了RyRs最初作为植物生物碱靶点被发现的故事,以及它们在心肌和骨骼肌兴奋-收缩偶联中的核心作用,还有正在进行的针对一类名为RycalsTM的新型药物的临床试验,这类药物可抑制病理性细胞内钙泄漏。此外,这些专利还突出了RyR领域的问题、争议和未来方向。