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| Targets |
Repressor element-1 silencing transcription factor (REST), also known as Neuron-Restrictive Silencer Factor (NRSF). REST is a transcriptional repressor that binds to RE1 (Repressor Element 1) sequences in DNA and suppresses the expression of neuronal genes in non-neuronal cells and neural progenitors. X5050 is a REST inhibitor with an EC50 of 2.1 microM, promoting REST degradation and reducing its protein levels.
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| ln Vitro |
A dose-dependent reduction in the REST isoform in protein level is induced by X5050 (100 µM, 1 day)[1].
In vitro, X5050 has an EC50 of 2.1 microM for REST inhibition. The compound induces a dose-dependent decrease in REST isoform protein levels at concentrations of 50-100 microM, leading to a 50% REST reduction. By degrading REST, it relieves repression of its target genes, which include many neuron-specific genes. This property makes it a useful tool for promoting neurogenesis or neuronal differentiation in cell culture. |
| ln Vivo |
In the pathogenic context of HD, X5050 (2 x 2µl of 20 mM) exhibits activity[1].
As a REST inhibitor, X5050 has been studied for its potential to promote neurogenesis (the generation of new neurons) in vivo. By reducing REST levels, it can de-repress neuronal genes, which may have therapeutic potential for conditions like stroke, spinal cord injury, and neurodegenerative diseases. It has also been studied in the context of cancer, as REST can act as an oncogene in certain tumors. Specific detailed in vivo efficacy data is not provided in standard literature. |
| Enzyme Assay |
A standard non-cellular (cell-free) assay for REST inhibitors is not common, as REST is a transcription factor that works by binding to DNA rather than having enzymatic activity. Researchers would typically use an Electrophoretic Mobility Shift Assay (EMSA) or a DNA-binding ELISA to test if X5050 directly affects REST's DNA-binding activity, but the compound's primary mechanism involves promoting protein degradation, which is a cellular process.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: NSCs. Tested Concentrations: 100 µM. Incubation Duration:One day. Experimental Results: Induced a dosedependent decrease in the 122 kDa longer REST isoform. X5050's activity is validated in cells using Western blot and reporter gene assays. Cells (e.g., SH-SY5Y neuroblastoma cells) are treated with X5050 (0-100 microM). Protein lysates are subjected to Western blotting with a REST antibody to confirm a dose-dependent decrease in REST protein levels. A second approach is to use a REST luciferase reporter plasmid (RE1-Luc) transfected into cells; X5050 treatment should increase luciferase activity as REST repression is relieved. The reported EC50 is 2.1 microM. |
| Animal Protocol |
Animal/Disease Models: 12weeks old male C57Bl6 mice[1].2
Doses: 2 x 2µl of 20 mM in 10% DMSO in water. Route of Administration: Intraventricular injection. Experimental Results: Increased BDNF expression. A decrease in Darpp32 and Snap25 expression was found by QRT-PCR in the lesioned striatum as compared with the contralateral striatum. Dramatically increased the levels of Bdnf II splice variant (exon II containing variant) while Bdnf IV levels were not Dramatically changed. For in vivo studies, X5050 is typically administered to animal models of neurological disease or injury, such as a mouse model of stroke (e.g., middle cerebral artery occlusion, MCAO) or traumatic brain injury (TBI). The compound is administered, often via intraperitoneal (IP) injection or oral gavage. Endpoints include measuring the expression of REST target genes in the brain by qPCR, assessing neural stem cell proliferation and differentiation by immunohistochemistry (e.g., BrdU, NeuN, DCX), and evaluating functional recovery using behavioral tests. |
| ADME/Pharmacokinetics |
X5050 is a small molecule with a molecular weight of 309.32 and a molecular formula of C17H15N3O3. It is highly soluble in DMSO (100 mg/mL). For in vivo use, it is typically formulated in vehicles like DMSO:PEG300:Tween80:Saline. The compound is stable as a powder for 3 years at -20degC and for 2 years at 4degC. In solvent, it can be stored at -80degC for 6 months or -20degC for 1 month. Specific PK parameters like half-life (t1/2) and oral bioavailability are not detailed in the literature.
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| Toxicity/Toxicokinetics |
Specific toxicological data for X5050 is not available in the reference literature. As a compound that reduces REST protein levels, on-target toxicity would be related to the functions of REST. In the adult brain, REST is important for protecting neurons from stress and injury, so reducing it could potentially make neurons more vulnerable to excitotoxicity or oxidative stress. However, in the context of cancer, where REST is overexpressed, inhibiting it may have anti-tumor effects. General lab safety precautions for handling chemical inhibitors should be used.
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| References | |
| Additional Infomation |
X5050 is a REST inhibitor.
X5050 is a research chemical tool used to inhibit the transcription factor REST. REST is a master regulator of neural gene expression, and its activity is critical for maintaining the undifferentiated state of neural stem cells and for protecting adult neurons from stress. Dysregulation of REST is implicated in various diseases, including Huntington's disease, epilepsy, medulloblastoma, and breast cancer. X5050 allows researchers to study the consequences of REST inhibition in these contexts. It is not approved for any clinical use and is strictly for preclinical research. The CAS number is 2404756-81-4. |
| Molecular Formula |
C17H15N3O3
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|---|---|
| Molecular Weight |
309.3193
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| Exact Mass |
309.111
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| CAS # |
2404756-81-4
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| PubChem CID |
146301742
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| Appearance |
White to light yellow solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
23
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| Complexity |
431
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O([H])C1=C([H])C([H])=C([H])C([H])=C1C1=NC2C([H])=C([H])C(C(N([H])OC([H])([H])C([H])=C([H])[H])=O)=C([H])C=2N1[H]
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| InChi Key |
RGROIKJLROTDCR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H15N3O3/c1-2-9-23-20-17(22)11-7-8-13-14(10-11)19-16(18-13)12-5-3-4-6-15(12)21/h2-8,10,21H,1,9H2,(H,18,19)(H,20,22)
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| Chemical Name |
2-(2-hydroxyphenyl)-N-prop-2-enoxy-3H-benzimidazole-5-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (323.29 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2329 mL | 16.1645 mL | 32.3290 mL | |
| 5 mM | 0.6466 mL | 3.2329 mL | 6.4658 mL | |
| 10 mM | 0.3233 mL | 1.6164 mL | 3.2329 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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