ISX 9 is a potent inducer of adult neural stem cell differentiation[1]. ISX 9 activates Ca2+ influx through both voltage-gated Ca2+ channels and NMDA receptors and increases neuroD expression[2]. ISX 9 is usually used for research related to neurogenesis, neuropsychiatric disorders, and circadian rhythm disorders[3][4].
In vitro, ISX 9 (10μM; 4 days) enhances circadian amplitude in synchronized mouse embryonic fibroblasts[5]. ISX 9 (1.25-5μM; 24-48h) dose-dependently promotes KGF and Ang-1 secretion in mesenchymal stem cells[6].
In vivo, ISX 9 (20mg/kg/day; i.p.; 12 days) reversed chronic intermittent ethanol exposure-induced enhancement of fear memory retrieval and restored structural and functional plasticity of ventral dentate gyrus granule cell neurons in male Wistar rats during protracted abstinence[7].
References:
[1] Schneider JW, Gao Z, Li S, et al. Small-molecule activation of neuronal cell fate. Nat Chem Biol. 2008;4(7):408-410.
[2] Petrik D, Jiang Y, Birnbaum SG, et al. Functional and mechanistic exploration of an adult neurogenesis-promoting small molecule. FASEB J. 2012;26(8):3148-3162.
[3] Bettio LEB, Gil-Mohapel J, Patten AR, et al. Effects of Isx-9 and stress on adult hippocampal neurogenesis: Experimental considerations and future perspectives. Neurogenesis (Austin). 2017;4(1):e1317692.
[4] Koh SH, Liang AC, Takahashi Y, et al. Differential Effects of Isoxazole-9 on Neural Stem/Progenitor Cells, Oligodendrocyte Precursor Cells, and Endothelial Progenitor Cells. PLoS One. 2015;10(9):e0138724.
[5] Li H, Ou J, Li Y, et al. ISX-9 potentiates CaMKIIδ-mediated BMAL1 activation to enhance circadian amplitude. Commun Biol. 2022;5(1):750.
[6] Tian Y, Deng Q, Yang X, et al. ISX-9 Promotes KGF Secretion From MSCs to Alleviate ALI Through NGFR-ERK-TAU-β-Catenin Signaling Axis. Stem Cells Transl Med. 2024;13(3):255-267.
[7] Staples MC, Herman MA, Lockner JW, et al. Isoxazole-9 reduces enhanced fear responses and retrieval in ethanol-dependent male rats. J Neurosci Res. 2021;99(11):3047-3065.
ISX 9 是成体神经干细胞分化的有效诱导剂[1]。ISX 9 通过电压门控钙通道和NMDAR激活钙离子内流,并增加NeuroD表达[2]。ISX 9通常用于神经发生、神经精神疾病及昼夜节律紊乱相关研究[3][4]。
体外实验中,ISX 9(10μM;4天)可增强同步化小鼠胚胎成纤维细胞的昼夜节律振幅[5]。ISX 9(1.25-5μM;24-48小时)剂量依赖性地促进间充质干细胞分泌KGF和Ang-1[6]。
体内实验中,ISX 9(20mg/kg/天;腹腔注射;12天)可在雄性Wistar大鼠的长期乙醇戒断期间逆转慢性间歇性乙醇暴露诱导的恐惧记忆增强,并恢复腹侧齿状回颗粒细胞神经元的结构和功能可塑性[7]。
















