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化合物 AT 7519 hydrochloride salt,AT7519 Hydrochloride
  • 化合物 AT 7519 hydrochloride salt,AT7519 Hydrochloride

化合物 AT 7519 hydrochloride salt|T1778|TargetMol

價格 171 392 653
包裝 1mg 5mg 10mg
最小起訂量 1mg
發(fā)貨地 上海
更新日期 2024-09-29
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產(chǎn)品詳情

中文名稱:化合物 AT 7519 hydrochloride salt英文名稱:AT7519 Hydrochloride
CAS:902135-91-5品牌: TargetMol
產(chǎn)地: 美國保存條件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
純度規(guī)格: 99.9%產(chǎn)品類別: 抑制劑
貨號: T1778
2024-09-29 化合物 AT 7519 hydrochloride salt AT7519 Hydrochloride 1mg/171RMB;5mg/392RMB;10mg/653RMB 171 TargetMol 美國 Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. 99.9% 抑制劑

Product Introduction

Bioactivity

名稱AT7519 Hydrochloride
描述AT7519 Hydrochloride (AT7519 HCl) is a multi-CDK inhibitor for CDK1, 2, 4, 6 and 9.
細(xì)胞實驗Cells are incubated with different concentrations of AT7519 for 24 or 48 hours at 37°C. Cell viability is assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrasodium bromide (MTT) dye absorbance. DNA synthesis is measured by tritiated thymidine uptake (3H-TdR). Apoptosis is assessed by using Annexin V/PI staining. The percentage of cells undergoing apoptosis is defined as the sum of early apoptosis (Annexin V-positive cells) and late apoptosis (Annexin V-positive and PI-positive cells(Only for Reference)
激酶實驗In vitro Kinase Assays: Kinase assays for CDK1, CDK2 and GSK3-β are all carried out in a radiometric filter binding format. Assays for CDK5 are in DELFIA format and for CDKs 4 and 6 in ELISA format. For CDKs 1 and 2, the relevant CDK and 0.12 μg/mL Histone H1 are incubated in 20 mM MOPS, pH 7.2, 25 mM β-glycerophosphate, 5 mM EDTA, 15 mM MgCl2, 1 mM sodium orthovanadate, 1 mM DTT, 0.1 mg/mL BSA, 45 μM ATP (0.78 Ci/mmol) and different concentrations of AT7519 for 2 or 4 hours respectively. For GSK3-β, the relevant enzyme and 5 μM glycogen synthase peptide 2 along with 10 mM MOPS pH 7.0, 0.1 mg/mL BSA, 0.001% Brij-35, 0.5% glycerol, 0.2 mM EDTA, 10 mM MgCl2, 0.01% β-mercaptoethanol, 15 μM ATP (2.31 Ci/mmol) and different concentrations of AT7519 are incubated for 3 hours. Assay reactions are stopped by adding an excess of orthophosphoric acid and filtered using Millipore MAPH filter plates. The plates are then washed, scintillant added and radioactivity measured by scintillation counting on a Packard TopCount. For CDK5, CDK5/p35 and 1 μM of a biotinylated Histone H1 peptide (Biotin-PKTPKKAKKL) are incubated in 25 mM Tris-HCl, pH 7.5, 2.5 mM MgCl2, 0.025% Brij-35, 0.1 mg/mL BSA, 1 mM DTT, 15 μM ATP and different concentrations of AT7519 for 30 minutes. Assay reactions are stopped using EDTA, transferred to Neutravidin-coated plates and phosphorylated peptide quantified by means of a rabbit phospho-cdk1 substrate polyclonal antibody and DELFIA europium-labelled anti-rabbit IgG secondary antibody using time-resolved fluorescence at λex=335 nM, λem=620 nM. For CDK 4 and 6 assays, plates are coated with GST- pRb769-921 and blocked with Superblock. CDK4 or 6 is incubated with 15 mM MgCl2, 50 mM HEPES, pH 7.4, 1 mM DTT, 1 mM EGTA, pH 8.0, 0.02% Triton X-100, 2.5% DMSO and different concentrations of AT7519; the reaction is initiated by addition of ATP. After 30 minutes, reactions are stopped by the addition of 0.5 M EDTA pH 8.0.Plates are then washed and incubated for one hour with the primary antibody (anti- p-Rb Serine 780) diluted in Superblock followed by secondary antibody (alkaline phosphatase linked anti-rabbit) for a further hour. Plates are developed using the Attophos system and fluorescence read on a Spectramax Gemini plate reader at excitation 450 nm and emission 580 nm. In all cases, IC50 values are calculated from replicate curves, using GraphPad Prism software.
體外活性AT7519是一種與ATP競爭的CDK抑制劑,對CDK1的Ki值為38nM。除了對GSK3β(IC50=89nM)有活性外,AT7519對所有非CDK激酶均無活性。在多種人類腫瘤細(xì)胞系中表現(xiàn)出強(qiáng)大的抗增殖活性,IC50值從MCF-7的40nM到SW620的940nM不等,這與CDK1和CDK2的抑制一致。[1] AT7519在48小時內(nèi)對多發(fā)性骨髓瘤(MM)細(xì)胞系產(chǎn)生劑量依賴性細(xì)胞毒性,IC50值從0.5μM到2μM不等,對MM.1S(0.5μM)和U266(0.5μM)細(xì)胞系最為敏感,對MM.1R(>2μM)耐藥性較強(qiáng)。它不對周圍血單個核細(xì)胞(PBMNC)產(chǎn)生細(xì)胞毒性。AT7519能部分克服IL6和IGF-1提供的增殖優(yōu)勢以及骨髓基質(zhì)細(xì)胞(BMSCs)的保護(hù)作用。AT7519快速促使RNA聚合酶II CTD在絲氨酸2和絲氨酸5位點(diǎn)的去磷酸化,導(dǎo)致轉(zhuǎn)錄抑制,部分促成了對MM細(xì)胞的AT7519誘導(dǎo)的細(xì)胞毒性。通過下調(diào)GSK-3β磷酸化促進(jìn)GSK-3β的激活,也為AT7519誘導(dǎo)的凋亡提供了幫助,這一過程與轉(zhuǎn)錄抑制無關(guān)。[2]
體內(nèi)活性每日兩次給予AT7519(9.1 mg/kg)可以導(dǎo)致HCT116和HT29結(jié)腸癌異種移植模型中,無論是早期還是晚期的皮下腫瘤退化。[1] AT7519治療(15 mg/kg)抑制了人類MM異種移植小鼠模型中的腫瘤生長,并通過增加caspase 3激活,延長了小鼠的中位總生存時間。[2]
存儲條件Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
溶解度Ethanol : 28 mg/mL (66.87 mM), Heating is recommended.
H2O : 1 mg/mL (2.38 mM), Heating is recommended.
DMSO : 40 mg/mL (95.53 mM), Sonication is recommended.
關(guān)鍵字Inhibitor | Apoptosis | inhibit | AT-7519 | AT7519 Hydrochloride | AT7519 | AT-7519 Hydrochloride | CDK | AT 7519 Hydrochloride | Cyclin dependent kinase | AT 7519
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關(guān)鍵字: AT7519 HCl|||AT 7519 hydrochloride salt|TargetMol

公司簡介

TargetMol Chemicals Inc. 總部位于馬薩諸塞州波士頓,致力于為全球生化領(lǐng)域科學(xué)家的研究提供專業(yè)的產(chǎn)品和服務(wù)。TargetMol?品牌的客戶群分布于40多個國家和地區(qū),已發(fā)展成為全球知名的化合物庫和小分子化合物研究供應(yīng)商。 TargetMol?可提供160多種滿足不同需求的化合物庫,以及多種類型的生化試劑產(chǎn)品,包括12000多種抑制劑、16000多種天然產(chǎn)物和各類多肽、抗體、生命科學(xué)試劑盒等,此外,我們還建設(shè)有CADD(計算機(jī)輔助藥物設(shè)計)研究中心、藥理實驗室、藥化合成平臺三大技術(shù)中心,全方位滿足客戶的定制需求。 憑借我們優(yōu)質(zhì)的產(chǎn)品和服務(wù)、快速高效的全球供應(yīng)鏈和專業(yè)的技術(shù)支持,我們將有效幫助您縮短研發(fā)周期,取得更成功的結(jié)果。
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