ISX-9  (Synonyms: Isoxazole 9)

ISX-9 (Isoxazole 9) is a potent inducer of adult neural stem cell differentiation. ISX-9 activates Ca²⁺ influx through both voltage-gated Ca²⁺ channels and NMDA receptors and increases neuroD expression. ISX-9 also induces cardiomyogenic differentiation of Notch-activated epicardium-derived cells (NECs)^[1][2][3]. In Vitro: ISX-9 promotes neurogenesis in vivo, enhancing the proliferation and differentiation of hippocampal subgranular zone (SGZ) neuroblasts, and the dendritic arborization of adult-generated dentate gyrus neurons. At 2.5-20 μM, ISX-9 has been shown to dose-dependently trigger neurogenesis and block gliogenesis in adult rat hippocampal stem cells through a calcium-activated signaling pathway dependent on myocyte-enhancer factor 2-dependent gene expression^[1].
Molecular exploration of ISX-9-induced regulation of neurogenesis (via FACS and microarray of SGZ stem and progenitor cells) suggested the involvement of the myocyte-enhancer family of proteins (Mef2)^[1]. In Vivo: ISX-9 (20 mg/kg; for 12 days; mice) treatment improves hippocampal function. ISX-9 enhances spatial memory ability in the Morris water maze test. ISX-9 enhances hippocampal neurogenesis and memory in vivo, and its effects are reliant on Mef2^[1].

ISX-9 (20 μM; for 7 days) can induce generated cardiac progenitor cells (CPCs) starting fromhuman-induced pluripotent stem cells (hiPSCs)^[1].
ISX-9 (20 μM) induces CPCs to secrete extracellular vesicles (EV)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

CPC^ISX-9-derived EV reversed cardiac remodeling in infarcted mice^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

234.27

C₁₁H₁₀N₂O₂S

832115-62-5

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• [1]. Wanling Xuan, et al. miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart. Stem Cells Int. 2019 Nov 11;2019:3726392. doi: 10.1155/2019/3726392. eCollection 2019.  [Content Brief]

  [2]. Maria Magdalena Barreca, et al. Mesenchymal and Induced Pluripotent Stem Cells-Derived Extracellular Vesicles: The New Frontier for Regenerative Medicine? Cells. 2020 May 8;9(5):1163.  [Content Brief]