| 名称 | Ilorasertib |
| 描述 | Ilorasertib (ABT-348) (ABT-348) is an ATP-competitive multitargeted kinase inhibitor, which inhibits Aurora A/Aurora B/Aurora C (IC50s: 120 nM/7 nM/1 nM). It also suppresses RET tyrosine kinase, PDGFRβ, and Flt1 (IC50s: 7 nM, 3 nM, and 32 nM). |
| 细胞实验 | Noncycling primary HUVEC are used to assess the effect of Ilorasertib on nonproliferating cells. Cells (35,000/well) are seeded in growth medium in a 96-well tissue culture plate, and after 2 days, the medium is changed and the cells are treated with Ilorasertib. After an additional 3 days, cell viability is measured with Cell TiterGlo reagent [2]. |
| 动物实验 | For flank xenograft models, cells are suspended in PBS, mixed with Matrigel (phenol red-free) in a ratio of 1:4 (v/v), and inoculated into the flank of female SCID/beige mice (5 million cells per site). Inoculated mice are randomized into groups of 10, and treatment is initiated when mean tumor volume is approximately 0.4 cm^3 or 0.5 cm^3. Tumor growth in the flank is assessed by measuring tumor size with calipers and calculating volume using the formula (L × W2/2). Study groups are terminated before tumor volume reaches 3 cm^3. Inhibition of tumor growth is assessed at the time the vehicle-treated group is terminated by calculating the ratio of the mean volume of the test drug group to the mean volume of the untreated (control) group (T/C) and calculating the percentage of inhibition of control [(1 ? T/C) × 100]. The dosing formulation of test agents is prepared by stepwise addition, with mixing, of the following reagents: EtOH, Tween 80, polyethylene glycol 400, and 2% hydroxypropyl methylcellulose (2:5:20:73, v/v). The dosing volume is 10 mL/kg [2]. |
| 体外活性 | 除了针对Aurora激酶外，Ilorasertib还是VEGFR和PDGFR激酶家族的强效抑制剂，并在较小程度上抑制Src家族的胞质酪氨酸激酶。Ilorasertib能够依赖浓度地增加两种NSCLC细胞系展现多倍体的程度和数量（EC50: 5, 10 nM）。Ilorasertib对表达BCR-ABL的CML细胞以及表达Gleevec抗性BCR-ABL T315I突变的细胞显示出抗增殖活性（IC50: 47, 260 nM）[2]。 |
| 体内活性 | Ilorasertib 在子宫水肿模型中有效抑制 VEGF 反应（ED50：0.2 mg/kg，静脉注射）。 Ilorasertib (25 mg/kg, s.c.) 可抑制从移植白血病模型获得的循环肿瘤细胞中的组蛋白 H3 磷酸化。 Ilorasertib（20 mg/kg，口服）可抑制人类异种移植模型中已形成肿瘤的生长并导致晚期肿瘤消退[2]。 Ilorasertib 在实体和血液异种移植模型中每周一次静脉、微型泵或肠胃外给药后显示出显着的抗肿瘤功效[3]。 |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 75 mg/mL (153.52 mM), Sonication is recommended.
10% DMSO+90% Saline : < 7.5 mg/mL (15.35 mM), Lower concentrations may be soluble, but exact solubility limit is unknown.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 7.5 mg/mL (15.35 mM), Solution.
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| 关键字 | VEGFR3 | VEGFR2 | VEGFR1 | VEGFR | Vascular endothelial growth factor receptor | RET | Platelet-derived growth factor receptor | PDGFRβ | PDGFR | MDS | Inhibitor | inhibit | Ilorasertib | histone H3 phosphorylation | H460 cells | H1299 | FLT1 | cRET | AuroraKinase | Aurora Kinase | Aurora C | Aurora B | Aurora A | anti-tumor | antiproliferative activity | AML | ABT348 | ABT 348 |
| 相关产品 | glycine | Gilteritinib | Ribociclib | Lenvatinib | Chloramphenicol | Thymoquinone | Regorafenib | Pazopanib | Sorafenib | Pexidartinib | Nintedanib esylate | Albendazole |
| 相关库 | 抑制剂库 | 抗癌活性化合物库 | 经典已知活性库 | 已知活性化合物库 | 临床失败化合物库 | 激酶抑制剂库 | 抗肝癌化合物库 | 膜蛋白靶向化合物库 | 药物功能重定位化合物库 | 酪氨酸激酶分子库 | 抗癌临床化合物库 | 抗癌药物库 |