基于片段的CK-571的结构-活性关系分析显示,非相互作用的组驱动光滑肌肉肌质素选择性
Sharad Kumar Suthar1, Tamás Jernei1, Csilla Kurdi2
1Motorpharma Limited, Batthyány utca 54, H-1015, Budapest, Hungary; Printnet Limited, Kisgömb utca 25-27, H-1135, Budapest, Hungary.
European journal of medicinal chemistry
|January 10, 2026
概括
研究人员确定了CK-571的关键结构特征,这些特征增强了其对光滑肌肉肌素-2 (SMM) 的效能和选择性,为开发喘和COPD治疗方法提供了新的框架.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 药物发现 药物发现 药物发现
背景情况:
- 光滑肌肉肌肉蛋白-2 (SMM) 是喘和COPD的治疗点.
- 选择性SMM抑制是很困难的,因为保存的肌酸氨酸-2异型.
- CK-571是一种强效和选择性的SMM抑制剂,向全位.
研究的目的:
- 使用基于碎片的结构-活动关系 (SAR) 分析来分解CK-571.
- 定义单个CK-571段在SMM抑制中的作用.
- 了解非相互作用组如何影响连接体的强度和选择性.
主要方法:
- 对CK-571.1的基于碎片的SAR分析.
- 生物化学测试来测量SMM抑制.
- 对CK-571具有SMM约束力的结构分析.
主要成果:
- 隔离的异二烯酸盐和-基基组是不活跃的.
- 一个甲基组和暴露于溶剂的二基组显著增加了CK-571的功效 (高达100倍).
- 这些增强组与SMM蛋白没有直接相互作用.
结论:
- 非相互作用的灵活组对于优化对保持目标的联结体强度和选择性至关重要.
- CK-571的功效受到看似不涉及的结构元素的显著影响.
- 这项研究为开发改善的SMM向治疗呼吸道疾病提供了框架.
相关概念视频
Overview of Myosin Structure and Function
6.3K
Myosins are a family of molecular motor proteins, first identified in the skeletal muscles, where they are responsible for muscle contraction. Along with their role in muscle contraction, these proteins also play a role in the intracellular transport of molecules and vesicles. There are twenty-four classes of myosins based on their domain sequence and organization. Of the twenty-four, six classes (Myosin I, Myosin II, Myosin V, Myosin VI, Myosin VII, and Myosin X) have been well...
6.3K
Actin and Myosin in Muscle Contraction
21.1K
Actin and myosin are contractile proteins that form the sarcomere found in skeletal muscle tissues for regulating muscle contraction. Actin, a globular contractile protein, interacts with myosin for muscle contraction. The skeletal tissue appears striped or striated under a microscope due to the repeated arrangement of contractile proteins actin and myosin along the length of myofibrils. Dark A bands and light I bands repeat along myofibrils, and the alignment of myofibrils in the cell causes...
21.1K
The Role of Actin and Myosin in Non-muscle Cells
4.5K
Actin and myosin or actomyosin filaments also play a significant role in cells other than those involved in muscle contraction (which occurs within the sarcomere of muscle cells). The mechanism of non-muscle cell contractile bundles was first observed in Dictyostelium and Acanthamoeba. In non-muscle cells, two bundles are commonly found: stress fibers and actomyosin adherence belts. These contractile bundles are smaller and less organized than the ones found in muscle cells. They are held...
4.5K
Structure and Organization of Smooth Muscles
8.4K
Smooth muscle tissue is a type of muscle tissue that can be found lining various vital organs in the human body, including the lungs, blood vessels, digestive tract, and respiratory tract. This type of tissue is responsible for regulating the movements of these organs, playing crucial roles in the functioning of various systems, including the vascular, digestive, respiratory, and urinary systems.
Structure of smooth muscle cell
Smooth muscle cells are spindle-shaped with tapering ends and a...
Structure of smooth muscle cell
Smooth muscle cells are spindle-shaped with tapering ends and a...
8.4K
Smooth Muscle Contraction
7.2K
Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
7.2K
Introduction to Actin
6.3K
Actin is a highly conserved cytoskeletal protein found abundantly in eukaryotic cells. It constitutes 10% weight of the total cellular protein in muscle cells, while in non-muscle cells, it is lower and makes up around 1–5 percent of the total cell protein. Actin found in the unicellular amoebae and complex multicellular animals is around 80% similar, demonstrating their conservation over a billion years of evolution. Actin coding genes are conserved within species and across...
6.3K


