| Identification | Back Directory | [Name]
ISX 9 | [CAS]
832115-62-5 | [Synonyms]
ISX 9
CS-1582
Isoxazole 9
Isoxazole
(ISX-9)
ISX 9(Isoxazole 9)
Isoxazole 9 (ISX-9)
Neuronal Differentiation Inducer III
ISX-9;ISX 9;NEURONAL DIFFERENTIATION INDUCER III
N-Cyclopropyl-5-(2-thienyl)-3-isoxazolecarboxamide
3-IsoxazolecarboxaMide, N-cyclopropyl-5-(2-thienyl)-
N-Cyclopropyl-5-(2-thienyl)-1,2-oxazole-3-carboxamide
N-Cyclopropyl-5-(thiophen-2-yl)isoxazole-3-carboxaMide | [Molecular Formula]
C11H10N2O2S | [MDL Number]
MFCD04133937 | [MOL File]
832115-62-5.mol | [Molecular Weight]
234.27 |
| Chemical Properties | Back Directory | [Boiling point ]
468.1±35.0 °C(Predicted) | [density ]
1.39±0.1 g/cm3(Predicted) | [storage temp. ]
-20° | [solubility ]
Soluble in DMSO (up to 60 mg/ml) or in Ethanol (up to 16 mg/ml). | [form ]
solid | [pka]
13.60±0.20(Predicted) | [color ]
Tan | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months. | [InChI]
InChI=1S/C11H10N2O2S/c14-11(12-7-3-4-7)8-6-9(15-13-8)10-2-1-5-16-10/h1-2,5-7H,3-4H2,(H,12,14) | [InChIKey]
SYENTKHGMVKGAQ-UHFFFAOYSA-N | [SMILES]
O1C(C2SC=CC=2)=CC(C(NC2CC2)=O)=N1 |
| Hazard Information | Back Directory | [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 Ca2+ 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. | [Synthesis]
GENERAL STEPS: Ethyl 5-(thiophen-2-yl)isoxazole-3-carboxylate (220 mg, 1 mmol) was dissolved in anhydrous ethanol (5 mL), followed by the addition of cyclopropylamine (285 mg, 5 mmol). The reaction mixture was sealed and heated at 80 °C for 24 hours. After completion of the reaction, it was cooled to room temperature and the reaction was quenched by the addition of water (1 mL). The resulting white crystalline solid, N-cyclopropyl-5-(thiophen-2-yl)isoxazole-3-carboxamide (150 mg, 64% yield) was collected by vacuum filtration. The product NMR hydrogen spectrum (400 MHz, d6-DMSO) data were as follows: δH 8.85 (1H, d), 7.83 (1H, d), 7.76 (1H, d), 7.24 (1H, d), 7.18 (1H, s), 2.83 (1H, m), 0.58-0.71 (4H, m). | [storage]
Store at -20°C | [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 |
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