MSN-125 is an inhibitor of Bax and Bak oligomerization, with an IC50 of 4μM[1]. Bax and Bak are key proteins in the apoptosis process[2]. Bax and Bak oligomerization increases the permeability of the mitochondrial outer membrane (MOMP), leads to the release of pro-apoptotic factors such as cytochrome c, thereby initiating the apoptosis program[3]. MSN-125 inhibits the oligomerization of Bax and Bak, prevents the increase of MOMP, and inhibits cell apoptosis[4]. MSN-125 is usually used to study the molecular mechanisms of apoptosis, especially in the fields of cancer and neuroprotection[5][6].
In vitro, MSN-125(5-10μM; 27h) inhibited cell death in HCT-116 or BMK cells treated with actinomycin D (ActD) or staurosporine (STS) and protected primary cortical neurons from glutamate excitotoxicity[1].
References:
[1] Niu X, Brahmbhatt H, Mergenthaler P, et al. A Small-Molecule Inhibitor of Bax and Bak Oligomerization Prevents Genotoxic Cell Death and Promotes Neuroprotection. Cell Chem Biol. 2017;24(4):493-506.e5.
[2] Pena-Blanco A, Garcia-Saez AJ. Bax, Bak and beyond - mitochondrial performance in apoptosis. FEBS J. 2018;285(3):416-431.
[3] Yamazaki T, Galluzzi L. BAX and BAK dynamics control mitochondrial DNA release during apoptosis. Cell Death Differ. 2022;29(6):1296-1298.
[4] Jensen K, WuWong DJ, Wong S, Matsuyama M, Matsuyama S. Pharmacological inhibition of Bax-induced cell death: Bax-inhibiting peptides and small compounds inhibiting Bax. Exp Biol Med (Maywood). 2019;244(8):621-629.
[5] Zhang Z, Hou L, Liu D, Luan S, Huang M, Zhao L. Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges. Acta Pharm Sin B. 2024;14(6):2378-2401.
[6] Spitz AZ, Gavathiotis E. Physiological and pharmacological modulation of BAX. Trends Pharmacol Sci. 2022;43(3):206-220.
MSN-125是一种Bax和Bak寡聚化的抑制剂，其IC50为4μM[1]。Bax和Bak是细胞凋亡过程中的关键蛋白[2]。Bax和Bak的寡聚化可增加线粒体外膜的通透性（MOMP），导致细胞色素C等促凋亡因子的释放，从而启动细胞凋亡程序[3]。MSN-125通过抑制Bax和Bak的寡聚化，阻止线粒体外膜通透性（MOMP）的增加，从而抑制细胞凋亡[4]。MSN-125通常用于研究细胞凋亡的分子机制，特别是在癌症和神经保护领域[5][6]。
在体外实验中，MSN-125（5-10μM；24小时）能够抑制经放线菌素D（ActD）或司他霉素（STS）处理的HCT-116或BMK细胞的细胞死亡，并保护原代皮层神经元免受谷氨酸兴奋毒性损伤[1]。