D4476
作者：齐岳
发布时间：2023-08-30
09:00:45
点击数：
产品名称：D4476
产品描述：
| 产品描述 | D4476 is an effective, selective, and cell-permeant CK1 (casein kinase 1) inhibitor( IC50=300 nM in a cell-free assay). |
| 靶点活性 | CK1 (casein kinase 1):300 nM |
| 体外活性 | D4476 (10 μM) effectively inhibits CK1 and ALK5 with the activities of about 7% and 22% versus control group, respectively. In H4IIE hepatoma cells, D4476 specifically inhibits the phosphorylation of endogenous forkhead box transcription factor O1a (FOXO1a) on Ser322 and Ser325, without affecting the phosphorylation of other sites.[1] D4476 induces cytotoxicity in ANBL6, INA6 and RPMI8226 lines; MM1S and U266 lines are less sensitive; and OPM1 line is totally resistant. High concentrations (50 μM) D4476 induced toxicity in all multiple myeloma (MM) lines. In MM cells, D4476 increases the protein levels of TP53, P27, and FADD, as well as the cell cycle progression and induction of apoptosis.[2] Treatment of leukemia stem cells (LSCs) with D4476 shows highly selective killing of LSCs over normal HSPCs.[3] |
| 激酶实验 | CK1 kinase assay: All protein kinase assays (25 μL) are carried out at room temperature (21℃). Assays are performed for 40 min using a Biomek 2000 Laboratory Automation Workstation in a 96-well format. The concentrations of magnesium acetate and [γ-33P]ATP (800 cpm/pmol) in the assays are 10 mM and 0.1 mM, respectively. Assays are initiated with MgATP and stopped by the addition of 5 μL of 0.5 M orthophosphoric acid. Aliquots are then spotted on to P30 ?ltermats, washed four times in 75 mM phosphoric acid to remove ATP, once in methanol, then dried and counted for radioactivity. CK1 δ (5-20 m-units), diluted in 20 mM Hepes, pH 7.5, 0.15 M NaCl, 0.1 mM EGTA, 0.1% (v/v) Triton X-100, 5 mM dithiothreitol, 50% (v/v) glycerol, is assayed against the peptide RRKDLHDDEEDEAMSITA in an incubation containing 20 mM Hepes, pH 7.5, 0.15 M NaCl, 0.1 mM EDTA, 5 mM DTT, 0.1% (v/v) Triton X-100 and 0.5 mM substrate peptide. |
| 细胞实验 | MM cells are seeded in triplicate into 96-well plates in 100 μL culture media. D4476 is added to each well at concentrations of 0, 5, 10, 20, 30, 40, and 50 μM in another 100 μL culture media. Cell viability is measured with MTT at the 72 h drug exposure. Absorbance is measured at 570 nm with spectrophotometer.(Only for Reference) |
| 别名 | D 4476, Casein Kinase I Inhibitor |
| 分子量 | 398.41 |
| 分子式 | C23H18N4O3 |
| CAS No. | 301836-43-1 |
存储
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
DMSO: 39.8 mg/mL (100 mM)
Ethanol: 19.9 mg/mL (50 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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公司介绍：
西安齐岳生物科技有限公司是集化学科研和定制与一体的高科技化学公司。业务范围包括化学试剂和产品的研发、生产、销售等。涉及产品为通用试剂的分销、非通用试剂的定制与研发，涵盖生物科技、化学品、中间体和化工材料等领域。
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