ISX 9 Chemical Properties

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).

pka

13.60±0.20(Predicted)

form 

solid

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

Safety Information

WGK Germany 

WGK 2

Storage Class

11 - Combustible Solids

ISX 9 Usage And Synthesis

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

+4°C

References

[1] DAVID PETRIK. Functional and mechanistic exploration of an adult neurogenesis-promoting small molecule[J]. FASEB Journal, 2012, 26 8: 3148-3162. DOI:10.1096/fj.11-201426
[2] JAY W SCHNEIDER. Small-molecule activation of neuronal cell fate[J]. Nature chemical biology, 2008, 4 7: 408-410. DOI:10.1038/nchembio.95
[3] OETJEN E. A small molecule differentiation inducer increases insulin production by pancreatic β cells[J]. Yearbook of Endocrinology, 2012, 26 1: 15. DOI:10.1016/j.yend.2012.03.059
[4] LING ZHANG . Small-molecule blocks malignant astrocyte proliferation and induces neuronal gene expression[J]. Differentiation, 2011, 81 4: Pages 233-242. DOI:10.1016/j.diff.2011.02.005
[5] ROUKNUDDIN QASIM ALI. Induction of sensory neurons from neuroepithelial stem cells by the ISX9 small molecule.[J]. American journal of stem cells, 2016, 5 1: 19-28.
[6] LUIS E.B. BETTIO . ISX-9 can potentiate cell proliferation and neuronal commitment in the rat dentate gyrus[J]. Neuroscience, 2016, 332: Pages 212-222. DOI:10.1016/j.neuroscience.2016.06.042

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