当前对黑素皮质素 4 受体激活的机制和药效动力学理解。
Current Mechanistic and Pharmacodynamic Understanding of Melanocortin-4 Receptor Activation.
机构信息
Rhythm Pharmaceuticals, Boston, MA 02116, USA.
出版信息
Molecules. 2019 May 16;24(10):1892. doi: 10.3390/molecules24101892.
Abstract
In this work we summarize our understanding of melanocortin 4 receptor (MC4R) pathway activation, aiming to define a safe and effective therapeutic targeting strategy for the MC4R. Delineation of cellular MC4R pathways has provided evidence for distinct MC4R signaling events characterized by unique receptor activation kinetics. While these studies remain narrow in scope, and have largely been explored with peptidic agonists, the results provide a possible correlation between distinct ligand groups and differential MC4R activation kinetics. In addition, when a set of small-molecule and peptide MC4R agonists are compared, evidence of biased signaling has been reported. The results of such mechanistic studies are discussed.
摘要
在这项工作中，我们总结了对黑素皮质素 4 受体 (MC4R) 途径激活的理解，旨在为 MC4R 的安全有效治疗靶向策略提供定义。细胞 MC4R 途径的描述为具有独特受体激活动力学的独特 MC4R 信号事件提供了证据。虽然这些研究的范围仍然很窄，并且主要是用肽激动剂进行探索的，但结果提供了不同配体群体和不同 MC4R 激活动力学之间可能的相关性。此外，当比较一组小分子和肽 MC4R 激动剂时，已经报道了偏向信号的证据。讨论了此类机制研究的结果。
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