| 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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| Other Sizes |
| Targets |
SMER18 targets the autophagy pathway, functioning as an mTOR-independent autophagy inducer. Unlike rapamycin, which induces autophagy through mTOR inhibition, SMER18 acts either independently or downstream of mTOR. The compound enhances the clearance of autophagy substrates including mutant huntingtin and A53T alpha-synuclein, which are associated with neurodegenerative diseases. By inducing autophagy, SMER18 promotes the degradation of aggregated proteins and damaged organelles through the lysosomal pathway. The compound shows additive protective effects with rapamycin.
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| ln Vitro |
In vitro studies demonstrate that SMER18 induces autophagy independently of rapamycin in mammalian cells. The compound enhances the clearance of autophagy substrates such as mutant huntingtin and A53T alpha-synuclein. SMER18 attenuates mutant huntingtin-fragment toxicity in Huntington's disease cell models. The compound has additive protective effects on the clearance and toxicity of mutant aggregate-prone proteins in vitro. As a positive regulator of autophagy, SMER18 promotes the degradation of protein aggregates that are associated with neurodegenerative diseases.
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| ln Vivo |
In vivo data shows that SMER18 attenuates mutant huntingtin-fragment toxicity in Drosophila melanogaster models of Huntington's disease. The compound's ability to induce autophagy and enhance clearance of autophagy substrates suggests potential for studying neurodegenerative diseases. By promoting the degradation of mutant huntingtin and alpha-synuclein, SMER18 may have protective effects in models of Huntington's disease and Parkinson's disease. The compound's mTOR-independent mechanism offers an alternative approach to autophagy modulation. Further in vivo studies are warranted.
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| Enzyme Assay |
The in vitro autophagy assay for SMER18 involves measuring autophagosome formation and autophagic flux in mammalian cells. Cells (e.g., HeLa, SH-SY5Y) are treated with varying concentrations of SMER18 (1-100 μM) for 4-24 hours. Autophagosome formation is assessed by LC3-II/I ratio by Western blot, LC3 puncta formation by immunofluorescence, or using GFP-LC3 reporter cells. Autophagic flux is measured using lysosomal inhibitors (chloroquine, bafilomycin A1) to assess LC3-II accumulation. Autophagy substrate clearance (mutant huntingtin, alpha-synuclein) is measured by Western blot or ELISA. Cell viability is assessed using MTT or CCK-8 assays. The mTOR-independent mechanism is confirmed by testing in the presence of mTOR inhibitors.
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| Cell Assay |
In vitro cellular assays for SMER18 typically use mammalian cell lines including HeLa, SH-SY5Y, or cells expressing mutant huntingtin or A53T alpha-synuclein. Cells are cultured in appropriate media and treated with the compound at concentrations of 1-100 μM for 4-72 hours. Autophagy is assessed by LC3-II/I ratio, LC3 puncta, and p62 levels by Western blot or immunofluorescence. Protein aggregate clearance (mutant huntingtin, alpha-synuclein) is measured by Western blot or ELISA. Cytotoxicity is assessed using MTT or LDH release assays. The additive protective effects with rapamycin are evaluated by co-treatment studies.
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| Animal Protocol |
In vivo animal studies for SMER18 involve Drosophila melanogaster models of Huntington's disease expressing mutant huntingtin fragments. Flies are fed SMER18 in their food at various concentrations (10-1000 μM) for 7-14 days. The compound's effect on mutant huntingtin-fragment toxicity is assessed by evaluating photoreceptor neuron degeneration in the fly eye using pseudopupil analysis or histological sectioning. Lifespan assays are performed to assess protective effects. Autophagy induction in vivo is confirmed by Western blot of LC3-II/I in fly heads. For mammalian studies, mouse models of neurodegenerative diseases would be used.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of SMER18 are not extensively reported. The compound has a molecular weight of 287.74 and molecular formula of C16H14ClNO2. It is soluble in DMSO (10 mM). The compound should be stored at -20°C for long-term preservation. Based on its physicochemical properties, the compound is expected to have reasonable membrane permeability and tissue penetration, including potential CNS penetration given its effects in Drosophila models. Further studies on oral bioavailability, plasma half-life, and brain penetration are needed.
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| Toxicity/Toxicokinetics |
Toxicological data for SMER18 is not extensively reported. As an autophagy inducer, the compound may affect cellular homeostasis and protein degradation pathways. The compound is for research use only and not for human therapeutic applications. Standard safety precautions should be followed when handling. For detailed toxicity information, specialized toxicological studies would need to be performed in appropriate animal models.
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| References | |
| Additional Infomation |
SMER18 is a research-grade compound with CAS number 944153-47-3. Its molecular formula is C16H14ClNO2 and molecular weight is 287.74. The compound is a small molecule enhancer of rapamycin and an mTOR-independent autophagy inducer. It enhances clearance of autophagy substrates including mutant huntingtin and A53T alpha-synuclein. The compound has additive protective effects on clearance of mutant aggregate-prone proteins. It attenuates toxicity in Huntington's disease models. This compound has not advanced to clinical trials and is not FDA-approved. It is strictly for research purposes only.
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| Molecular Formula |
C16H14CLNO2
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|---|---|
| Molecular Weight |
287.743
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| Exact Mass |
287.071
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| CAS # |
944153-47-3
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| PubChem CID |
877863
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
458.7±45.0 °C at 760 mmHg
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| Flash Point |
231.2±28.7 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.656
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| LogP |
3.88
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
20
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| Complexity |
362
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C/C(=C/C(=O)C1=CC=C(C=C1)Cl)/NC2=CC(=CC=C2)O
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| InChi Key |
SNEQASFEVWLKOJ-LUAWRHEFSA-N
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| InChi Code |
InChI=1S/C16H14ClNO2/c1-11(18-14-3-2-4-15(19)10-14)9-16(20)12-5-7-13(17)8-6-12/h2-10,18-19H,1H3/b11-9-
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| Chemical Name |
(Z)-1-(4-chlorophenyl)-3-(3-hydroxyanilino)but-2-en-1-one
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| Synonyms |
SMER-18 SMER 18 SMER18
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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 (~347.54 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.69 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 | 3.4754 mL | 17.3768 mL | 34.7536 mL | |
| 5 mM | 0.6951 mL | 3.4754 mL | 6.9507 mL | |
| 10 mM | 0.3475 mL | 1.7377 mL | 3.4754 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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