| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
The EC50 value of YTX-465 (1-10000 nM) for the rescue of alpha-synuclein (α-syn) toxicity is 0.013 μM [1]. 0.05 μM; 0–2 days) of YTX-465 recovers the growth of yeast expressing α-Syn [1]. In wild-type yeast producing OLE1, YTX-465 (0, 10, 40, 160, 640, 2500 nM; 4h) increases Ole1 protein levels in a concentration-dependent manner, indicating that YTX-465 generates a negative feedback loop [1]. Fat desaturation in wild-type yeast is lowered by YTX-465 (0, 0.03, 0.09, 0.27, 0.81 μM; 6 hours) in a concentration-dependent manner, with a 50% reduction at 0.03 μM [1]. In yeast of the wild type, YTX-465 (0.25 μM; 8 hours) decreases the desaturation index (DI) of all main classes of membrane phospholipids [1].
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| ln Vitro |
The EC50 value of YTX-465 (1-10000 nM) for the rescue of alpha-synuclein (α-syn) toxicity is 0.013 μM [1]. 0.05 μM; 0–2 days) of YTX-465 recovers the growth of yeast expressing α-Syn [1]. In wild-type yeast producing OLE1, YTX-465 (0, 10, 40, 160, 640, 2500 nM; 4h) increases Ole1 protein levels in a concentration-dependent manner, indicating that YTX-465 generates a negative feedback loop [1]. Fat desaturation in wild-type yeast is lowered by YTX-465 (0, 0.03, 0.09, 0.27, 0.81 μM; 6 hours) in a concentration-dependent manner, with a 50% reduction at 0.03 μM [1]. In yeast of the wild type, YTX-465 (0.25 μM; 8 hours) decreases the desaturation index (DI) of all main classes of membrane phospholipids [1].
YTX-465 rescued α-synuclein-induced toxicity in yeast with an EC₅₀ of 0.013 µM, restoring growth rates to approximately 40% of wild-type levels. [1] The compound inhibited yeast growth with a GI₅₀ of 0.181 µM in wild-type yeast not expressing α-synuclein. [1] In a yeast strain expressing human SCD1, YTX-465 showed no growth inhibition or fatty acid desaturation inhibition, indicating selectivity for yeast Ole1 over human SCD1. [1] In human iPSC-derived cortical neurons, YTX-465 was not tested; however, the SCD inhibitor CAY10566 (0.3 µM) reduced fatty acid desaturation indices for both C16 and C18 fatty acids after 8 days of treatment. [1] |
| Enzyme Assay |
A biochemical assay using rat liver microsomes (RLM) was performed to assess SCD1 inhibition. The assay used C17:0-CoA as a substrate to avoid interference from endogenous C18 substrates. Reactions were carried out in 100 µL volumes containing 100 mM NaPO₄ pH 7.4, 10 mM ATP, 1 mM free coenzyme A, and 2 mM NADPH. Inhibitors were pre-spotted in DMSO, followed by addition of RLM (50 µg/mL) in reaction mix. Reactions were initiated by adding C17:0-CoA (final 10 µM) and incubated for 30 minutes at room temperature before quenching with formic acid. Product formation was analyzed by rapid-fire mass spectrometry. YTX-465 showed no inhibition of SCD1 in this assay (IC₅₀ > 33 µM). [1]
In yeast, fatty acid desaturation was measured by gas chromatography with flame ionization detection after treating cells with YTX-465 for 6 hours. The desaturation index (unsaturated/saturated ratio) was calculated from C16 and C18 fatty acid methyl ester levels. YTX-465 reduced the desaturation index in a concentration-dependent manner, with a 50% reduction at 0.03 µM. [1] |
| Cell Assay |
Yeast growth assays were performed in synthetic media with 2% galactose to induce α-synuclein expression. Cultures were grown to mid-log phase, diluted, and treated with compound in 384-well plates. Growth was measured by OD₆₀₀ after 40 hours. Rescue was calculated as fold-change relative to DMSO-treated controls. [1]
For fatty acid analysis, yeast were treated with YTX-465 for 6 hours, harvested, and lipids were extracted. Fatty acids were hydrolyzed, derivatized, and analyzed by gas chromatography. [1] Lipidomics analysis was performed by LC-MS/MS on yeast pellets after treatment with YTX-465. Lipids were extracted using methanol/chloroform/water, and species were quantified by high-resolution mass spectrometry. [1] α-Synuclein-GFP localization was assessed by fluorescence microscopy after fixing yeast cells with paraformaldehyde. Images were analyzed for foci count and area using spot detection algorithms. [1] CPY trafficking was assessed by immunoblotting yeast lysates after treatment with YTX-465. Antibodies against CPY and Pgk1 (loading control) were used. [1] |
| References | |
| Additional Infomation |
YTX-465 is a 1,2,4-oxadiazole derivative that was found to rescue the toxicity of α-synuclein through yeast phenotypic screening. [1] It directly inhibits yeast Ole1 enzyme, reduces fatty acid desaturation, and reverses α-synuclein-induced vesicle transport defects and triglyceride accumulation. [1] In the rescue experiment, the concentration-effect curve of this compound was bell-shaped, with more significant growth inhibition at higher concentrations. [1] Supplementation with oleic acid and palmitoleic acid (products of Ole1 enzyme) reversed its effect. [1] YTX-465 did not inhibit human SCD1 enzyme in either biochemical or yeast experiments, indicating that it has species-specific pharmacological properties. [1]
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| Molecular Formula |
C25H26N6O3
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|---|---|
| Molecular Weight |
458.512344837189
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| Exact Mass |
458.206
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| Elemental Analysis |
C, 65.49; H, 5.72; N, 18.33; O, 10.47
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| CAS # |
2225824-53-1
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| PubChem CID |
134477586
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| Appearance |
White to off-white solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
723
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UNYSKYOVUXWBJG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H26N6O3/c1-16-20-9-8-19(14-21(20)30(2)28-16)23-27-25(34-29-23)18-10-12-31(13-11-18)22(32)15-26-24(33)17-6-4-3-5-7-17/h3-9,14,18H,10-13,15H2,1-2H3,(H,26,33)
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| Chemical Name |
N-[2-[4-[3-(1,3-dimethylindazol-6-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-2-oxoethyl]benzamide
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| Synonyms |
YTX 465; YTX-465; YTX465;
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~218.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1810 mL | 10.9049 mL | 21.8098 mL | |
| 5 mM | 0.4362 mL | 2.1810 mL | 4.3620 mL | |
| 10 mM | 0.2181 mL | 1.0905 mL | 2.1810 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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