- 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
calculate
LY-411575 Molarity Calculator
calculate
| 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.
ebiomall.com
>
>
>
>
>
>
>
>
>
>
>
如果要测量细胞表面2个受体的比率，最好用流式细胞仪来测量
跑到还有半小时的时候，跳出一个对话框：“analysiscannotproceed:notenoughsamplesdefined”，最后做出来的结果有扩增曲线但是没有熔解曲线，请各位大神帮忙解释一下。
荧光定量PCR较普通PCR不同的一点就是可以实时检测PCR扩增产物，从而可进行绝对定量或者相对定量。
半定量反转录－聚合酶链反应（semi-quantitative reverse transcription and polymerase Chain reaction ,SqRT-PCR）是近年来常用的一种简捷、特异的定量RNA测定方法，通过mRNA反转录成cDNA，再进行PCR扩增，并测定PCR产物的数量，可以推测样品中特异mRNA的相对数量。
定量RT-PCR（quantitative reverse transcription and polymerase Chain reaction ,qRT-PCR）是在用一步法或两步法，在PCR反应体系中加入荧光基团，利用荧光信号积累实时监测整个PCR进程，最后通过标准曲线对未知模板进行定量分析的方法。
半定量RT-PCR需要跑电泳，根据条带亮度的强弱来判断模板拷贝数的高低或者是表达量的高低，而定量RT-PCR则无需电泳可以实时监测整个PCR的全程并且由给出的Ct值及Standard Curve来判断gene拷贝数的高低。
PCR(聚合酶链式反应）是利用DNA在体外摄氏95°高温时变性会变成单链，低温（经常是60°C左右）时引物与单链按碱基互补配对的原则结合，再调温度至DNA聚合酶最适反应温度（72°C左右），DNA聚合酶沿着磷酸到五碳糖(5'-3')的方向合成互补链。
恒温PCR和实时荧光定量PCR的不同，是不同在实时荧光定量PCR的系统中加入了荧光染料（SYBR Green 或Taqman 探针等等）。以SYBR Green为例，这种染料可以结合在双链的DNA上，当PCR不断进行时，每一次退火生成的双链DNA也在增加，荧光染料结合也越多，荧光也越强。在机器中有一个探测荧光的探头，可以定量检测荧光的强度，转换成数值。这样就可以实时记录反映体系中DNA的反应情况。
荧光PCR更有优势，因为荧光PCR灵敏度高于恒温PCR，同样价格也高一些。
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。
暂无品牌问答
