- ￥1510 - 5790
- Solarbio
- 北京
- IP6350
- 2026年02月09日
企业认证
相关产品推荐更多 >
万千商家帮你免费找货
0 人在求购买到急需产品
- 详细信息
- 文献和实验
- 技术资料
- 保存条件：
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year
- 保质期：
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year
- 英文名：
PF-06751979
- 库存：
现询
- 供应商：
北京索莱宝科技有限公司
- CAS号：
1818339-66-0
- 规格：
10mg/5mg/1mg
| 规格： | 10mg | 产品价格： | ￥5790.0 |
|---|---|---|---|
| 规格： | 5mg | 产品价格： | ￥3790.0 |
| 规格： | 1mg | 产品价格： | ￥1510.0 |
| 基本信息 | |
| CAS | No.1818339-66-0 |
| 英文名称 | PF-06751979 |
| 分子式 | C18H19F2N5O3S2 |
| 分子量 | 455.5 |
| 溶解性 | Soluble in DMSO |
| 纯度 | ≥98% |
| 外观(性状) | Solid |
| 储存条件 | Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| SMILES | CC1CC2CSC(=NC2(CO1)C3=NC(=CS3)NC(=O)C4=NC=C(C=C4)OC(F)F)N |
| InChIKey | ZLZUHACSRMOLLV-RAALSFIWSA-N |
| InChI | InChI=1S/C18H19F2N5O3S2/c1-9-4-10-6-30-17(21)25-18(10，8-27-9)15-24-13(7-29-15)23-14(26)12-3-2-11(5-22-12)28-16(19)20/h2-3，5，7，9-10，16H，4，6，8H2，1H3，(H2，21，25)(H，23，26)/t9-，10-，18-/m0/s1 |
| PubChem CID | 118435360 |
| 靶点 | Beta-secretase (BACE1) |
| 通路 | Neuronal Signaling |
| 背景说明 | PF-06751979 是一种有效的，脑渗透性的 β-淀粉样前体蛋白裂解酶1 (BACE1) 抑制剂。 |
| 生物活性 | PF-06751979 is a potent， brain penetrant， β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor with an IC50 of 7.3 nM in BACE1 binding assay.[1] |
| IC50 | IC50: 7.3 nM (BACE1)， 194 nM (BACE2)[1] |
| In Vitro | PF-06751979 shows improved selectivity over BACE2 (IC50=194 nM) in binding (27-fold) relative to the literature examples and across multiple chemical series in BACE1 program. PF-06751979 also inhibits BACE1 and BACE2 in a fluorescent polarization (FP) assay with IC50s of 26.9 nM and 238 nM， respectively. PF-06751979 has excellent potency at BACE1 in binding or FP assay formats along with cellular activity looking at production of sAPPβ in H4 cells with an IC50 of 5 nM[1]. |
| 细胞实验 | PF-06751979 displays excellent brain penetration， potent in vivo efficacy， and broad selectivity over related aspartyl proteases including BACE2. Acute administration of PF-06751979 yields a robust dose-responsive and time-dependent reduction of cerebral spinal fluid (CSF) Aβx-40 with peak inhibition at 3 h of >77%. To determine if the reduction in brain and CSF Aβ is maintained during sustained exposure to PF-06751979， a 5 day subchronic study is executed， dosing once daily by subcutaneous (SC) administration (10 or 50 mg/kg/day). Brain and CSF samples are collected on day 5， following the last dose. PF-06751979 produces a dose-responsive and time-dependent inhibition of Aβ42 in mouse brain. At the 50 mg/kg/day dose， maximal brain lowering is 63% at 7 to 9 h. Administration of PF-06751979 (10 or 50 mg/kg/day for 5 days) produces a dose-responsive and time-dependent inhibition of Aβx-40 in mouse CSF resulting in 77% inhibition of CSF at 3 h post-final 50 mg/kg dose[1]. |
| 细胞实验 | The neuroglioma cell line H4 cells are grown in Dulbecco’s modified Eagle’s medium (DMEM) with 10% fetal bovine serum (FBS) and 200 mM glutamax. Cells are plated overnight in tissue culture treated Falcon 384-well plates at a cell density of 4500 cells/well in 50 μL of media. The next day， media is removed， and cells are washed once with PBS， after which 25 μL of media is placed in all wells， followed by the addition of the diluted PF-06751979 dose response curve. The highest concentration tested is 30 μM with 1% DMSO. Cells serving as the background controls receive 30 μM of a proprietary compound. Compounds are allowed to incubate with cells overnight in a 37°C incubator. Concurrently， 384-well black Nunc Maxisorp plates are also incubated overnight at 4°C with 10 μL of 4 μg/mL Aβ antibody in coating buffer (0.1 M sodium bicarbonate， pH 8.8 to 9.0)[1]. |
| 动物实验 | Mice[1] Male 129/sve wild-type mice (20-25 g) are in a nonfasted state prior to subcutaneous dosing with vehicle or PF-06751979 using a dosing volume of 10 mL/kg. The mice are dosed subcutaneously once a day for 5 days with PF-06751979 (10 or 50 mg/kg/day) or vehicle. The mice (n=5 per group) are then sacrificed at 1， 3， 5， 7， 14， 20， and 30 h postdose. Following cardiac puncture into ethylenediaminetetraacetic acid (EDTA)-containing tubes， whole blood samples (0.5-1.0 mL) are collected， and plasma is separated by centrifugation (1500× g for 10 min at 4°C). The generated plasma is distributed into separate tubes on wet ice for exposure measurements (50 μL) and Aβ analysis (remainder). CSF samples (8-12 μL) are obtained by cisterna magna puncture using a sterile 25 gauge needle and collected with a P-20 Eppendorff pipet. CSF samples are distributed into separate tubes on dry ice for exposure measurements (3 μL) and Aβ analysis (remainder). Whole brain is removed and divided for exposure measurements (cerebellum) and Aβ analysis (left and right hemispheres)， weighed， and frozen on dry ice. Prior to the assay， all samples are stored at -80°C[1]. |
| 激酶实验 | Both BACE1 and BACE2 enzymatic activity is measured with the aid of an optimized synthetic peptide substrate biotin-GLTNIKTEEISEISYEVEFR-C[Oregon green]KK-OH. Upon cleavage of the peptide substrate， a decrease in fluorescence polarization is measured. Compounds are diluted by half log in 100% DMSO 11 times with a top concentration of 10mM in a 384-well polypropylene plate. The 100% DMSO dose response curve is then added to a 384-well black assay plate as 0.150 μL per well. The final working top concentration is 0.1 mM， and the DMSO concentration is 1%. A volume of 7.5 μL of BACE substrate is then added in assay buffer (100 mM sodium acetate， pH to 4.5 with glacial acetic acid， 0.001% Tween 20). The background wells in column 1 of the 384-well assay plate receive 7.5 μL of assay buffer. The reaction is started with the addition of 7.5 μL of BACE1 or BACE2 enzyme in assay buffer to all wells except the background wells in column 1. The final concentration of peptide substrate is 150 nM， and the final concentration of BACE1 and BACE2 enzyme is 0.15 and 2.5 nM， respectively. The assay plate is sealed and incubated at 37°C for 3 or 1 h (BACE1 or BACE2， respectively). After incubation， 15 μL of stop solution (1.5 μM streptavidin in Dulbecco’s PBS) is added to all wells， and the plate is read. Percent effect values for each concentration of compound are calculated based on fluorescence polarization (FP) readings in the 100% effect control wells containing no enzyme and the 0% effect control wells containing no compound. Curve-fitting analysis utilizing concentrations and percent effect values for a given compound is plotted， and the IC50 is determined using a sigmoidal four-parameter fit algorithm[1]. |
| 数据来源文献 | [1]. ONeill BT， et al. Design and Synthesis of Clinical Candidate PF-06751979: A Potent， Brain Penetrant， β-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor Lacking Hypopigmentation. J Med Chem. 2018 May 24;61(10):4476-4504. |
| 单位 | 瓶 |
风险提示：丁香通仅作为第三方平台，为商家信息发布提供平台空间。用户咨询产品时请注意保护个人信息及财产安全，合理判断，谨慎选购商品，商家和用户对交易行为负责。对于医疗器械类产品，请先查证核实企业经营资质和医疗器械产品注册证情况。
文献和实验相关实验
基因敲除模型：NLRP3−/−、GSDMD−/−、caspase-1/11−/−小鼠、RACK1ΔMΦ。 4、检测内容：LDH（乳酸脱氢酶）释放实验检测细胞毒性、ELISA 检测细胞因子分泌、WB 检测、免疫沉淀（IP）、pull down、质谱、EST12 晶体结构、共聚焦显微镜、小鼠结核感染模型等。 研究结果： 1、EST12（Rv1579c）诱导 GSDMD 介导的巨噬细胞焦亡 表达纯化 40 种 RD 区编码蛋白，通过 LDH 释放实验，发现 EST12（Rv1579c）具有明显的巨噬
！！ xiongran 我有做过相关的工作，可以和你讨论一下。本来IFN-r是可以通过诱导启动子含有GAS element的基因表达的，这条通路是通过JAK-STAT的经典通路。但是我查过资料，IP10的启动子中并不包含GAS element。但是这并不妨碍，IP10的确通过JAK-STAT信号通路被IFNr诱导，具体机制我没有查文献，因为这个不是我研究的重点，不过我可以给你几张信号传导的图片以及一些文献，希望对你有帮助！ xiongran
578475733 因最近要做蛋白激酶C在糖尿病方面的实验，求助各位高手有没有蛋白激酶C信号通路的图片，最好带注解，十分感谢。 石依信念 我也想要～～～～ 黑胡桃 [img]data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAskAAAGdCAYAAADgwu6RAAAgAElEQVR4Aey9B7xdxZXmu04
技术资料暂无技术资料 索取技术资料
IP6350 PF-06751979 神经信号通路 索莱宝
￥1510 - 5790
