期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 14, 期 5, 页码 606-613出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.3c00029
关键词
-
The mitogen-activated protein kinase (MAPK) signaling cascade is essential for regulating various cellular activities across eukaryotes. In this study, a novel class of irreversible MAP2K7 inhibitors was designed and synthesized, with promising in vitro potency and selectivity, as well as favorable cellular activity. These compounds show potential as powerful tools for studying pediatric T cell acute lymphoblastic leukemia (T-ALL).
The mitogen-activated protein kinase signaling cascade is conserved across eukaryotes, where it plays a critical role in the regulation of activities including proliferation, differentiation, and stress responses. This pathway propagates external stimuli through a series of phosphorylation events, which allows external signals to influence metabolic and transcriptional activities. Within the cascade, MEK, or MAP2K, enzymes occupy a molecular crossroads immediately upstream to significant signal divergence and cross-talk. One such kinase, MAP2K7, also known as MEK7 and MKK7, is a protein of great interest in the molecular pathophysiology underlying pediatric T cell acute lymphoblastic leukemia (T-ALL). Herein, we describe the rational design, synthesis, evaluation, and optimization of a novel class of irreversible MAP2K7 inhibitors. With a streamlined one-pot synthesis, favorable in vitro potency and selectivity, and promising cellular activity, this novel class of compounds wields promise as a powerful tool in the study of pediatric T-ALL. KEYWORDS: mitogen-activated protein kinases, drug discovery, small molecule inhibitors, lead optimization, covalent inhibitors, irreversible T cell acute MKK7
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据