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Purity: ≥98%
SMER28 is a small molecule activator (enhancer/modulator) of autophagy that acts via an mTOR-independent mechanism. It induces autophagy independent of rapamycin in mammalian cells and prevents the accumulation of amyloid beta peptide. The hallmarks of Alzheimer's disease are the aggregates of amyloid-β (Αβ) peptide and tau protein. Autophagy is one major cellular pathway leading to the removal of aggregated proteins. Induction of autophagy by small-molecule enhancers such as SMER28 greatly decreased the levels of Aβ peptide (apparent EC50 of ∼10 μM) and APP-CTF (apparent EC50 of ∼20 μM) in a γ-secretase-independent manner. Pharmacological inhibition of autophagy led to a significant accumulation of Aβ peptide and APP-CTF and diminished the effect of SMER28. Therefore, SMER28 may have therapeutic potential to be used for the treatment of Alzheimer's disease and other proteinopathies.
| ln Vitro |
Cell viability in SMER28 (5-200 μM; 24 hours) decreases with dose[4].
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| ln Vivo |
Mice survival is increased at 65 mg/kg of SMER28 (15-65 mg/kg; ih; daily, two days prior to irradiation and over the three days of irradiation) and is strongly protected against post-irradiation weight loss[5].
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| Cell Assay |
Cell Viability Assay[4]
Cell Types: MMS1 cells Tested Concentrations: 5, 25, 50, 75, 100, 150, 200 μM Incubation Duration: 24 hrs (hours) Experimental Results: demonstrated a dose dependent decline of cell viability. |
| Animal Protocol |
Animal/Disease Models: 14 to 16 weeks male mice (Balb/c)[5]
Doses: 15, 65 mg/kg Route of Administration: subcutaneous (sc) injection; two days before irradiation and during the three days of irradiation (total 5 days) Experimental Results: Dramatically protected against post- irradiation weight loss and enhanced survival of mice at 65 mg/kg. |
| References |
[1]. Renna M et al. Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases. J Biol Chem. 2010 Apr 9;285(15):11061-7.
[2]. Nekova TS, et al. Small molecule enhancers of rapamycin induce apoptosis in myeloma cells via GSK3A/Bpreferentially within a protective bone marrow microenvironment. Br J Haematol. 2014 Oct;167(2):272-4. [3]. Shen D et al. Novel cell- and tissue-based assays for detecting misfolded and aggregated protein accumulation within aggresomes and inclusion bodies. Cell Biochem Biophys. 2011 Jul;60(3):173-85. [4]. Koukourakis MI, et al. SMER28 is a mTOR-independent small molecule enhancer of autophagy that protects mouse bone marrow and liver against radiotherapy. Invest New Drugs. 2018 Oct;36(5):773-781. [5]. Tian Y et al. A small-molecule enhancer of autophagy decreases levels of Abeta and APP-CTF via Atg5-dependent autophagy pathway. FASEB J. 2011 Jun;25(6):1934-42. |
| Additional Infomation |
SMER 28 is a member of the class of quinazolines that is quinazoline which is substituted by a prop-2-en-1-ylnitrilo group and a bromo group at positions 4 and 6, respectively. It is a modulator of mammalian autophagy. It has a role as an autophagy inducer. It is a member of quinazolines, a secondary amino compound and an organobromine compound.
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| Molecular Formula |
C11H10BRN3
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| Molecular Weight |
264.12
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| Exact Mass |
263.006
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| Elemental Analysis |
C, 50.02; H, 3.82; Br, 30.25; N, 15.91
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| CAS # |
307538-42-7
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| Related CAS # |
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| PubChem CID |
1560402
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| Appearance |
Solid powder
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| Melting Point |
169 °C
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| LogP |
2.412
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
15
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| Complexity |
222
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C=CCNC1=C2C=C(Br)C=CC2=NC=N1
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| InChi Key |
BCPOLXUSCUFDGE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H10BrN3/c1-2-5-13-11-9-6-8(12)3-4-10(9)14-7-15-11/h2-4,6-7H,1,5H2,(H,13,14,15)
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.47 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 (9.47 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 (9.47 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 | 3.7862 mL | 18.9308 mL | 37.8616 mL | |
| 5 mM | 0.7572 mL | 3.7862 mL | 7.5723 mL | |
| 10 mM | 0.3786 mL | 1.8931 mL | 3.7862 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.
Effect of SMER28 on levels of Aβ peptide and APP-CTF.FASEB J.2011 Jun;25(6):1934-42. |
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SMER28 and starvation lead to reduced levels of Aβ peptide and APP-CTF through autophagy pathway.FASEB J.2011 Jun;25(6):1934-42. |
SMER28-induced clearance of Aβ40 and APP-CTF is dependent on Atg5.FASEB J.2011 Jun;25(6):1934 -42. |
Beclin1 and Ulk1 regulate basal, but not SMER28-induced, clearance of Aβ40 and APP-CTF.FASEB J.2011 Jun;25(6):1934-42. |
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SMER28 induced cocompartmentalization of APP-CTF and LC3-II.A) N2a-APP cells were treated for 6 h with SMER28 (50 μM), and whole-cell lysates were fractionated by sucrose gradient.FASEB J.2011 Jun;25(6):1934-42. |
Autophagy as a protective pathway for neurodegenerative diseases.J Biol Chem.2010 Apr 9;285(15):11061-7. |
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