Mapping TRPM7 Function by NS8593.
Mapping TRPM7 Function by NS8593.
复制标题
DOI：
10.3390/ijms21197017
复制
发表时间：
2020-09-23
影响因子：
5.6
通讯作者：
Gudermann T
中科院分区：
文献类型：
--
作者：
Chubanov V;Gudermann T
瞬时受体电位阳离子通道M亚家族成员7（TRPM7）是一种广泛表达的膜蛋白，它形成一个与胞质蛋白激酶相连的通道。在动物模型中对TRPM7进行基因失活揭示了TRPM7在早期胚胎发育、免疫反应以及锌离子（Zn²⁺）、镁离子（Mg²⁺）和钙离子（Ca²⁺）的机体平衡中的关键作用。TRPM7成为一个新的治疗靶点，因为TRPM7的功能失常与缺氧性神经元死亡、组织纤维化、肿瘤进展和巨大血小板疾病有关。最近，几个实验室已经鉴定出能够调节TRPM7通道或激酶活性的药理化合物。在其他小分子中，NS8593被定义为TRPM7通道的一种强效负门控调节剂。因此，几个研究小组应用NS8593来研究由TRPM7调节的细胞通路。在此，我们总结这一研究领域的进展。特别是，在评估TRPM7的成药性方面已经达到了两个显著的里程碑。首先，几个实验室证明NS8593处理可靠地反映了通过TRPM7基因失活操作的细胞的显著表型。其次，已经表明NS8593使我们能够探究TRPM7在人类疾病动物模型中的治疗潜力。总体而言，这些使用NS8593的研究可以作为针对TRPM7的药物的临床前评估的蓝图。
The transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a ubiquitously expressed membrane protein, which forms a channel linked to a cytosolic protein kinase. Genetic inactivation of TRPM7 in animal models uncovered the critical role of TRPM7 in early embryonic development, immune responses, and the organismal balance of Zn2+, Mg2+, and Ca2+. TRPM7 emerged as a new therapeutic target because malfunctions of TRPM7 have been associated with anoxic neuronal death, tissue fibrosis, tumour progression, and giant platelet disorder. Recently, several laboratories have identified pharmacological compounds allowing to modulate either channel or kinase activity of TRPM7. Among other small molecules, NS8593 has been defined as a potent negative gating regulator of the TRPM7 channel. Consequently, several groups applied NS8593 to investigate cellular pathways regulated by TRPM7. Here, we summarize the progress in this research area. In particular, two notable milestones have been reached in the assessment of TRPM7 druggability. Firstly, several laboratories demonstrated that NS8593 treatment reliably mirrors prominent phenotypes of cells manipulated by genetic inactivation of TRPM7. Secondly, it has been shown that NS8593 allows us to probe the therapeutic potential of TRPM7 in animal models of human diseases. Collectively, these studies employing NS8593 may serve as a blueprint for the preclinical assessment of TRPM7-targeting drugs.
登录
查看更多内容
影响因子：
4.6
作者：
Cai N;Bai Z;Nanda V;Runnels LW
通讯作者：
Runnels LW
影响因子：
4.6
作者：
Carvacho I;Ardestani G;Lee HC;McGarvey K;Fissore RA;Lykke-Hartmann K
通讯作者：
Lykke-Hartmann K
影响因子：
8
作者：
Brandao, Katherine;Deason-Towne, Francina;Zhao, Xiaoyun;Perraud, Anne-Laure;Schmitz, Carsten
通讯作者：
Schmitz, Carsten
影响因子：
6
作者：
Chubanov V;Schäfer S;Ferioli S;Gudermann T
通讯作者：
Gudermann T
影响因子：
--
作者：
Chen WL;Barszczyk A;Turlova E;Deurloo M;Liu B;Yang BB;Rutka JT;Feng ZP;Sun HS
通讯作者：
Sun HS