Waixenicin A, a marine-derived TRPM7 inhibitor: a promising CNS drug lead.

Waixenicin A, a marine-derived TRPM7 inhibitor: a promising CNS drug lead. Acta Pharmacol Sin. 2020 Sep 29;: Authors: Sun HS, Horgen FD, Romo D, Hull KG, Kiledal SA, Fleig A, Feng ZP Abstract Ion channels are the third largest class of targets for therapeutic drugs. The pharmacology of ion channels is an important research area for identifying new treatment options for human diseases. The past decade or so has seen increasing interest in an ion channel protein belonging to the transient receptor potential (TRP) family, namely the melastatin subfamily member 7 (TRPM7), as an emerging drug target. TRPM7 is a bifunctional protein with a magnesium and calcium-conducting divalent ion channel fused with an active kinase domain. TRPM7 is ubiquitously expressed in human tissues, including the brain, and regulates various cell biology processes such as magnesium and calcium homeostasis, cell growth and proliferation, and embryonic development. TRPM7 provides a link between cellular metabolic status and intracellular calcium homeostasis in neurons due to TRPM7's unique sensitivity to fluctuating intracellular Mg·ATP levels. Thus, the protein plays a key role in ischemic and hypoxic neuronal cell death and brain injury, and is one of the key nonglutamate mechanisms in cerebral ischemia and stroke. Currently, the most potent and specific TRPM7 inhibitor is waixenicin A, a xenicane diterpenoid from the Hawaiian soft coral Sarcothelia edmondsoni...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research