價格 | ¥285 | ¥668 | ¥1090 |
包裝 | 1mg | 5mg | 10mg |
最小起訂量 | 1mg |
發(fā)貨地 | 上海 |
更新日期 | 2024-12-12 |
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 |
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。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 |
相關(guān)產(chǎn)品 | L-Glutamic acid | Metronidazole | 5-Fluorouracil | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | Myricetin | Sorafenib | L-Ascorbic acid | Acetylcysteine | Salicylic acid | Sodium 4-phenylbutyrate |
相關(guān)庫 | 神經(jīng)保護(hù)化合物庫 | 抑制劑庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | 神經(jīng)退行性疾病化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 |
成立日期 | 2013-04-18 (12年) | 注冊資本 | 566.265100萬人民幣 |
員工人數(shù) | 100-500人 | 年營業(yè)額 | ¥ 1億以上 |
主營行業(yè) | 天然產(chǎn)物,生化試劑,分子生物學(xué),分子砌塊,生物技術(shù)服務(wù) | 經(jīng)營模式 | 貿(mào)易,工廠,試劑,定制,服務(wù) |
產(chǎn)品名稱 | 價格 | 公司名稱 | 報價日期 | |
---|---|---|---|---|
詢價 |
VIP3年
|
上海嘉定區(qū)澄瀏公路52號
|
2025-01-16 | |
詢價 |
VIP9年
|
上海芮暉化工科技有限公司
|
2025-01-14 | |
詢價 |
VIP1年
|
陜西西化化學(xué)工業(yè)有限公司
|
2024-12-31 | |
詢價 |
VIP4年
|
湖北諾迪納生物技術(shù)有限公司
|
2024-12-19 | |
¥555.90 |
VIP1年
|
上海阿拉丁生化科技股份有限公司
|
2024-11-29 | |
詢價 |
南京百鑫德諾生物科技有限公司
|
2024-09-26 | ||
詢價 |
上海銳輝醫(yī)藥科技有限公司
|
2021-04-28 |