您好,欢迎来到试剂信息网! [登录] [免费注册]
试剂信息网
位置:首页 > 产品库 > SMER28
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
SMER28
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
SMER28图片
CAS NO:307538-42-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议
1g电议

产品介绍
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.
理化性质和储存条件
Molecular Weight (MW) 264.12
Formula C11H10BrN3
CAS No. 307538-42-7
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: ≥ 30 mg/mL
Water: N/A
Ethanol: N/A
Chemical Name 6-bromo-N-2-propen-1-yl-4-quinazolinamine
Synonyms SMER-28; SMER28; SMER 28
SMILES Code C=CCNC1=C2C=C(Br)C=CC2=NC=N1
实验参考方法
In Vitro

In vitro activity: 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.


Kinase Assay: Of 50,729 compounds tested in a high-throughput screen, a number of small molecule inhibitors and enhancers (SMERs) of the cytostatic effects of rapamycin were identified and subsequently analyzed in a secondary screen in mammalian cells by analyzing the clearance of A53T mutant α-synuclein (a good autophagy substrate) in the absence of rapamycin as putative modulators of autophagy. We confirmed that SMER10, SMER18, and SMER28 were positive regulators of autophagy acting independently of rapamycin. These SMERs increased autophagosome synthesis and enhanced the clearance of model autophagy substrates such as A53T α-synuclein and mutant huntingtin fragments. Autophagy induced by SMERs was mTOR-independent. Furthermore, these SMERs were protective in a Drosophila model of HD. Further screening of the structural analogs of these three SMERs identified 18 additional small molecules that enhanced the clearance of aggregate-prone protein.


Cell Assay: Cells were grown in 4-well slide chambers (Lab Tek; Nalge Nunc, Rochester, NY, USA) and fixed with 4% paraformaldehyde. Cells were then permeabilized in 0.1% Triton X-100 and stained with primary antibodies, followed by FITC-conjugated secondary antibodies. The coverslips were mounted by Prolong Gold antifade reagent with DAPI (Invitrogen, Carlsbad, CA, USA). The images were aquired using a confocal microscope and the LSM5 3.2 software.

In Vivo
Animal model
Formulation & Dosage
References FASEB J. 2011 Jun;25(6):1934-42; J Biol Chem. 2010 Apr 9;285(15):11061-7.