Description
ISX9 (832115-62-5) promotes neurogenesis in vivo enhancing the proliferation and differentiation of hippocampal subgranular zone neuroblasts and enhances memory.1?Induces robust neuronal differentiation in adult neural stem cells.2?Increases insulin production by pancreatic β cells.3?ISX9 blocks malignant astrocyte proliferation, downregulates their astrocyte character, induces reentry into the cell cycle and upregulates neuronal gene expression.4 Induces sensory neurons from neuroepithelial stem cells.5 Potentiates cell proliferation and neuronal commitment in the rat dentate gyrus.6
Uses
N-Cyclopropyl-5-(thiophen-2-yl)isoxazole-3-carboxamide was shown to exhibit regulatory effects towards the expression of pH sensing G protein-coupled receptor-68 and is now a new drug target for ischemic heart disease.
Definition
ChEBI: N-cyclopropyl-5-thiophen-2-yl-3-isoxazolecarboxamide is a heteroarene and an aromatic amide.
General Description
A cell-permeable isoxazole compound that selectively induces robust neuronal differentiation (Effective concentration = 20 μM) in various stem/progenitor cells. Induces insulin expression, and activates ERK signaling and histone acetylation in MIN6 pancreatic β cells. The underlying excitation-neurogenesis signaling is comprised of, at least in part, an initial NMDA receptor- and L-type chanenels-mediated Ca
2+ influx, followed by an activation of CaMKII, phosphorylation/nuclear export of the MEF2 repressor HDAC5, the subsequent de-repression of MEF2, and the eventual activation of the HDAC-MEF2 epigenetic/transcriptional regulatory network.
References
1) Petrik et al. (2012), Functional and mechanistic exploration of an adult neurogenesis-promoting small molecule; FASEB J., 26 3148
2) Schneider et al. (2008), Small-molecule activation of neuronal cell fate; Nat. Chem. Biol., 4 408
3) Dioum et al. (2011), A small molecule differentiation inducers increases insulin production by pancreatic β cells; Proc. Natl. Acad. Sci. USA, 108 20713
4) Zhang et al. (2011), Small molecule blocks malignant astrocyte proliferation and induces neuronal gene expression; Differentiation, 81 233
4) Ali et al. (2016) Induction of sensory neurons from neuroepithelial stem cells by the ISX9 small molecule; Am. J. Stem. Cells 5 19
5) Bettio et al. (2016) ISX-9 can potentiate cell proliferation and neuronal commitment in the rat dentate gyrus; Neuroscience, 332 212
