- BMS-708163 (Avagacestat)
- DAPT (GSI-IX)
- BMS 299897
- YO-01027 (Dibenzazepine, DBZ)
- Flurizan
- Semagacestat (LY450139)
| LY-411575Gamma secretase inhibitor |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
- View current batch:
- Purity = 99.10%
- COA (Certificate Of Analysis)
- HPLC
- NMR (Nuclear Magnetic Resonance)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
| Description | LY411575 is a potent γ-secretase inhibitor with IC50 value of 0.078 nM and 0.082 nM for membrane and cell-based, respectively. | |||||
| Targets | γ-secretase | Notch S3 cleavage | ||||
| IC50 | 0.078 nM (membrane-based) 0.082 nM (cell-based) | 0.39 nM | ||||
| Kinase experiment [1]: | |
Inhibitory activities | Procedures for measuring γ-secretase activity in membranes prepared from HEK293 cells expressing APP. Intact HEK293 cells expressing either APP or NE were treated with various concentrations of LY-411,575 for 4 h at 37℃. In the case of cells expressing NE, cells were lysed, the cell lysates were separated on a 4-12% NuPAGE gel, and the processed NICD fragment was detected via Western blot with a cleavage site-specific antibody. The inhibition of NICD production was quantified by spot densitometric analysis using FluorChem. In the case of cells expressing APP, the conditioned medium was collected, centrifuged at 10,000×g for 5 min to remove cell debris, and stored at -20℃ prior to the determination ofAβ levels. Aβ40 and -42 produced in HEK293 membrane- and cell-based assays, as well as plasma Aβ40 and cortex Aβ40 from TgCRND8 mice, were analyzed without pretreatment using an electrochemiluminescence detection-based immunoassay. Plasma Aβ42 was measured by enzyme-linked immunosorbent assay. A commercially available enzyme-linked immunosorbent assay kit was used to measure cortex Aβ42. |
| Cell experiment [1]: | |
Cell lines | HEK293 cells expressing human APP carrying both the Swedish and London mutations or NE. |
Preparation method | Soluble in DMSO > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions | 4 h. |
Applications | In HEK293 cells expressing human APP or N E, LY-411,575 inhibits Aβ40 and NICD production with IC50 values of 0.082 and 0.39 nM, respectively. |
| Animal experiment [1]: | |
Animal models | Six-week-old female TgCRND8 or male C57BL/6 mice. |
Dosage form | 1-10 mg/kg; dosed orally once/day for 5 or 15 days. |
Preparation method | Formulated as 10 mg/ml solutions in 50% polyethylene glycol, 30% propylene glycol, 10% ethanol and diluted in 0.4% methylcellulose for dosing. |
Applications | In TgCRND8 mice, LY-411,575 decreases brain and plasma Aβ40 and Aβ42. LY-411,575 (10 mg/kg) reduces weight of mice by 2 g. LY-411,575 induces a marked atrophy of the cortical zone of the thymus and reduces the amount of thymocyte cells. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Wong GT, Manfra D, Poulet FM, et al. Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem, 2004, 279(13): 12876-12882. | |
LY-411575 Dilution Calculator
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| Cas No. | 209984-57-6 | SDF | Download SDF |
| Synonyms | N/A | ||
| Chemical Name | (2S)-2-[[(2S)-2-(3,5-difluorophenyl)-2-hydroxyacetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide | ||
| Canonical SMILES | CC(C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)C(C4=CC(=CC(=C4)F)F)O | ||
| Formula | C26H23F2N3O4 | M.Wt | 479.48 |
| Solubility | ≥23.85 mg/mL in DMSO, ≥98.4 mg/mL in EtOH with ultrasonic, <2.54 mg/ml="" in="" h2o=""> | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
LY-411575 is a potent inhibitor of γ-secretase with IC50 value of 0.078 nM in membrane assay.[1]γ-Secertase is one of intramenbrane-cleaving aspartyl protease which cleaves many type-I membrane proteins and many of them have important biological functions. γ-Secretase is a multi-subunit protease and it contains presenilin, nicastrin, APH-1(Anterior Pharynx- defective 1) and PEN-2. Presenilin contains Asp258 and Asp385 embedded in the sixth and seventh transmembrane domain and forms the active site. The feature of being a membrane integrated protease complex makes it difficult to be purified as well as studying its mechanism.γ-secretase is responsible for the generation Aβfrom the amyloid precursor protein.γ-Secertase has been considered as an important drug target for Alzheimer"s disease.γ-Secertase also is responsible for Notch processing which is related to cancer such as leukemia.[2]LY-411,575 significantly inhibits theγ-secretase activity in vitro. LY-411,575 inhibits the production of Aβproduction with IC50 value of 0.078 nM in membrane-assay and 0.082 nM in cell-basedγ-secretase assays, respectively. LY-411,575 also affects the Notch pathway by inhibiting Notch S3 cleavage with IC50 value of 0.39 nM.[1] LY-411,575 treatment also significantly inhibited the Notch pathway by inhibiting the γ-secretase activity luciferase activity in primary KS cells. LY-411,575 also induced the apoptosis though Notch pathway inhibition in primary and immortalized Kaposi"s sarcoma (KS) tumor cells.[2]LY-411,575 decreases the levels of brain and plasma Aβ40 and -42 at 10 mg/kg oral doses.[1] LY-411,575 also decreases cortical Aβ40 levels in transgenic CRND8 mice with ED50 ≈ 0.6 mg/kg. LY-411,575 also induced significantly intestinal goblet cell hyperplasia and thymus atrophy by inhibiting Notch signaling pathway at higher doses in vivo.[3]References: 1.Wong GT, Manfra D, Poulet FM, Zhang Q, Josien H, Bara T, Engstrom L, Pinzon-Ortiz M, Fine JS, Lee HJ et al: Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem 2004, 279(13):12876-12882.2.Curry CL, Reed LL, Golde TE, Miele L, Nickoloff BJ, Foreman KE: Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi"s sarcoma tumor cells. Oncogene 2005, 24(42):6333-6344.3.Hyde LA, McHugh NA, Chen J, Zhang Q, Manfra D, Nomeir AA, Josien H, Bara T, Clader JW, Zhang L et al: Studies to investigate the in vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-di hydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY411,575) in the CRND8 mouse. J Pharmacol Exp Ther 2006, 319(3):1133-1143.
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一般说来，应选用口碑较好的经过大量客户实验验证的荧光定量PCR试剂盒，因为只有选对了试剂盒才能够做成漂亮的实验结果来，特别是对于一些珍贵的样品更不能因为节约一些蝇头小利而糟蹋了样品本身。OneShineSybrGreenpreMix试剂盒在研发之初就考虑到了一般科研环境中方方面面的影响，例如我们就光照强度、光照时间对本产品的影响做了严苛的实验论证，得到1ml本产品盛装于1.5ml离心管中放置在2000Lux光照强度下可以保存12h，超过12h产品性能则会下降。
OneShineSybrGreenpreMix这款试剂盒除了价格适中外，还主要有以下优点：
1、适用于RealTimePCR反应，可以快速、准确地对目的基因进行定量检测。
2、在2×OneShineSybrGreenpreMix中，预先混有SybrGreen，PCR体系配制时只需入模板、引物、ddH2O即可，操作方便快捷。
3、含有更耐高温并持续稳定的DNAPolymerase，可以维持更多的循环数，提供了选择循环数更大的空间。更大的Ct值选择范围就意味着可以支持微量目的基因检测，检测范围fM-nM。
4、反应的Buffer更适合，使反应的基线更水平，无荧光污染信号。使线性期更陡峭，避免了Ct值的无效浮动。使平台期更平直。也确保了引物与模板能够更特异地结合。
5、SybrGreen更耐高温更足量，确保只要扩增反应在进行，目的DNA双链在增加，就有线性强度的荧光产生。
6、dNTPs更足量，确保反应有更高的平台期荧光信号。
7、Mg2+浓度更适合，确保线性期有爆发式的目的DNA片段合成，提高了线性期反应体系的扩增系数和线性期的长度。
8、更高的仪器适配性，SybrGreen染料可以被各大主流仪器的激发光所激发，产生明亮的荧光信号，有利于仪器对信号的捕捉和处理。
我们的产品与市面上目前常见的一种产品相比较有如下区别：
A公司的产品没有熔解温度，或者熔解温度太高。但是A公司的产品Ct值出现略早，这是因为A公司使用了一种小分子量的DNA聚合酶，这种酶与模板和引物的结合较快和较松散，但是扩增的效率和扩增的特异性就不能保证了，类似于温水煮青蛙不温不火的；这种酶还有一个弱点就是不耐冻融。我们使用的是Taq酶，是一种分子量较大的DNA聚合酶，这种酶与模板和引物结合比较慢，但是慢工出细活，这种酶的特异性较好，一旦激活便呈现爆发式的扩增，类似于不鸣则已一鸣惊人。我们产品熔解温度是A公司不可比拟的，线性范围和斜率也是A公司不可比拟的。详见下图：
标准品的荧光强度和已知的浓度作图，可以得到一条标准曲线。而待测样本的荧光强度测出以后，就可以在标准曲线上算出样本浓度了。
国产的有上海宏石，枫岭，中山达安基因，上海科华生物，大约10-15万。
进口的有ABI公司的大约45万，罗氏诊断的大约40万，Bio-Rad的大约30万。
还需要反转录用的引物、定量PCR用的一对引物、荧光信号源（荧光染料或荧光标记的探针，看你用什么策略来做定量PCR）
报价要看你需要服务商提供什么服务，如果你只提供实验材料，要求服务商做以上全部工作，只检测一个指标（一个基因的表达水平变化），价格大约每个样品350-500元，多一个指标大约多90元。
一般至少做一组数据两个样品嘛，所以你按1000块一组样品预算吧。
两步法，是因为设计引物的时候把退火温度设为酶的工作温度，而且定量PCR的产物都很短，需要的时候都短，所以两步法更方便。三步法的话，花的时间长，不利于快速实验。
