Citations
1 publicationsPublications from researchers using this productDescription
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.
Protocol
| Cell experiment [1]: | |
Cell lines | MEF cells |
Preparation Method | For the real-time recording of PER2::LUC bioluminescence, 2.5×105 mPer2Luc MEF cells were seeded and then cultured for 48h with DMEM in 3.5cm dishes until confluent. The cells were then synchronized with 200nM dexamethasone for 1h, before the bioluminescence recording in serum-free DMEM medium supplemented with 200μM luciferin together with ISX 9 at 10μM. The cultures were recorded in a light-tight chamber containing photon multiplier tube recording (PMT) detector assemblies for continuous 4 days. Data including amplitude and period results, were processed with the LumiCycle Analysis software. Cell cultures were lysed for immunoblot analysis. |
Reaction Conditions | 10μM; 4 days |
Applications | ISX 9 increased PER2::LUC oscillations and DBP protein levels in synchronized MEF cells. |
| Animal experiment [2]: | |
Animal models | male Wistar rats |
Preparation Method | Two hundred and thirteen adult male Wistar rats were housed in a temperature-controlled (22°C) vivarium with ad libitum access to food and water and completed the study. Animals were set on a 12-hr light/ 12-hr dark cycle, with the light cycle beginning at 8:00p.m., in groups of two or three animals per cage unit. During chronic intermittent ethanol vapor exposure (CIE), 106 rats were exposed to cycles of ethanol vapor produced via vaporization of 95% ethanol in a heated flask that was immediately conveyed through controlled air flow to rat vapor chambers on a 14-hr on/10-hr off daily schedule for the duration of 7 weeks. The vapor flow rate was calibrated so as to achieve target blood alcohol levels (BALs) within the range of 125-250mg/dl. BALs were measured utilizing an Analox AM1 analyzer. Following 7 weeks of CIE, rats were forced withdrawn from CIE and experienced training of trace fear conditioning (TFC). A subset of these rats were tested for context and fear retrieval at three time points post training-early (24h), mid (10 days), and late abstinence (21 days). The remaining 107 rats served as air controls (Air; no CIE) and were housed in similar cages as the CIE rats without the vapor exposure. ISX 9 was prepared for injections with 25% HBC (2-hydrox ypropyl-β-cyclodextrin). Following 5 weeks of CIE, a subset of CIE (n=39) and Air (n=40) rats were injected with ISX 9 (i.p.; 20mg/kg body weight) once per day for 12 days. Subsequently, a subset of animals (21-day time point; n=20 Air, n=19 CIE) received one 5′-bromo-2-deoxyuridine (BrdU) injection (i.p.; 150mg/kg). Forty-eight hours after the last ISX 9 injection, or 72 hr after the last vapor session, CIE and Air rats were trained for Trace fear conditioning. |
Dosage form | 20mg/kg/day; i.p.; 12 days |
Applications | ISX 9 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. |
References: | |
Product Documents
Chemical Properties
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility
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