化合物AT9283 T3068

Product Introduction
Bioactivity


英文名: AT9283

描述: AT9283 (J-504568) 是一种多靶点激酶抑制剂，抑制多种实体瘤在体内外的生长和存活，有效抑制Aurora A/B，JAK2/3，Abl (T315I)，和Flt3，IC50值范围为 1-30 nM。

细胞实验: HCT 116 cells are cultured in DMEM + 10% FBS + GLUTAMAX I. Black 96-well flat-bottomed (clear) tissue culture treated plates are seeded in 200 μL of medium and incubated for approximately 16 hours at 37°C in a humidified atmosphere of 5% CO2 in air. Cells are treated with test compound at nine different concentrations (spanning 1 nM to 10 μM, plus DMSO vehicle control) and then incubated for 72 hours. Polyploidy morphological observations of the cells are then noted. The concentration of AT9283 required to produce a distinct polyploid phenotype is reported. Cells are seeded at a concentration of 75−100 cells/mL relevant culture media onto 6- or 24-well tissue culture plates and allowed to recover for 16 hours. Test compound (11 concentrations spanning 0.1 nM to 10 μM) or vehicle control (DMSO) is added to duplicate wells to give a final DMSO concentration of 0.1%. Following compound addition, colonies are allowed to grow between 10 and 14 days for optimum discrete colony counting. Colonies are fixed in 2 mL of Carnoys fixative (25% acetic acid, 75% MeOH) and stained in 2 mL of 0.4% w/v crystal violet. The numbers of colonies in each well is counted. IC50 values are calculated by sigmoidal dose-response (variable slope) IC50 curves using Prism Graphpad software. (Only for Reference)

激酶实验: Aurora A and Aurora B Kinase Assays: Assays for Aurora A and B are performed in a DELFIA format. Aurora A enzyme is incubated with AT9283 and 3 μM cross-tide substrate (biotin-CGPKGPGRRGRRRTSSFAEG) in 10 mM MOPS, pH 7, 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, and 2.5% DMSO. Aurora B enzyme is incubated with AT9283, 3 μM of the above substrate in 25 mM Tris, pH 8.5, 5 mM MgCl2, 0.1 mg/mL BSA, 0.025% Tween-20, 1 mM DTT, 15 μM ATP, and 2.5% DMSO. Reactions are allowed to proceed for 60 minutes and 45-90 minutes for Aurora A and Aurora B, respectively, before quenching with EDTA. The reaction mixtures are then transferred to a neutravidin-coated plate, and phosphorylated peptide is quantified by means of a phospho-specific antibody and a europium labeled secondary antibody using time-resolved fluorescence (excitation, 337 nm; emission, 620 nm). IC50 values for the control compounds are 92 nM (Aurora A assay) and 17 nM (Aurora B).

体外活性: 携带HCT116人结肠癌移植瘤的小鼠中,AT9283（15-20 mg/kg）能够抑制肿瘤生长.

体内活性: 在HCT116细胞中（IC50=30 nM）,AT9283抑制Aurora B 激酶活性,产生多倍体表现型,同时抑制集落形成。AT9283还能够显著抑制多种激酶,例如包括Aurora A（IC50=3 nM）, Aurora B（ IC50=3 nM）, JAK3（IC50=1.1 nM）, JAK2（IC50=1.2 nM ）和 Abl（IC50=4 nM）。

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 71 mg/mL (186.1 mM)
Ethanol : 22 mg/mL(57.7 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)


关键字: AT-9283 | Apoptosis | Cluster of differentiation antigen 135 | Janus kinase | Autophagy | inhibit | Bcr-Abl | Fms like tyrosine kinase 3 | FLT3 | J504568 | AT9283 | Aurora Kinase | AT 9283 | Inhibitor | J 504568 | JAK | CD135

相关产品: Meloxicam | TVB-3166 | JHU395 | VR23 | PI3K/Akt/mTOR-IN-2 | STAT3-IN-11 | Atractylenolide III | Maduramicin ammonium | 5-Fluorouracil | PD0166285

相关库: JAK-STAT Compound Library | Drug Repurposing Compound Library | Anti-Neurodegenerative Disease Compound Library | ReFRAME Related Library | Anti-Cancer Drug Library | Inhibitor Library | Kinase Inhibitor Library | Anti-Cancer Clinical Compound Library | Anti-Cancer Active Compound Library | Tyrosine Kinase Inhibitor Library

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注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途