| 名稱 | 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). |
| 細(xì)胞實(shí)驗(yàn) | 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]. |
| 動(dòng)物實(shí)驗(yàn) | 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]. |
| 體外活性 | 除了針對(duì)Aurora激酶外，Ilorasertib還是VEGFR和PDGFR激酶家族的強(qiáng)效抑制劑，并在較小程度上抑制Src家族的胞質(zhì)酪氨酸激酶。Ilorasertib能夠依賴濃度地增加兩種NSCLC細(xì)胞系展現(xiàn)多倍體的程度和數(shù)量（EC50: 5, 10 nM）。Ilorasertib對(duì)表達(dá)BCR-ABL的CML細(xì)胞以及表達(dá)Gleevec抗性BCR-ABL T315I突變的細(xì)胞顯示出抗增殖活性（IC50: 47, 260 nM）[2]。 |
| 體內(nèi)活性 | Ilorasertib 在子宮水腫模型中有效抑制 VEGF 反應(yīng)（ED50：0.2 mg/kg，靜脈注射）。 Ilorasertib (25 mg/kg, s.c.) 可抑制從移植白血病模型獲得的循環(huán)腫瘤細(xì)胞中的組蛋白 H3 磷酸化。 Ilorasertib（20 mg/kg，口服）可抑制人類異種移植模型中已形成腫瘤的生長(zhǎng)并導(dǎo)致晚期腫瘤消退[2]。 Ilorasertib 在實(shí)體和血液異種移植模型中每周一次靜脈、微型泵或腸胃外給藥后顯示出顯著的抗腫瘤功效[3]。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 55 mg/mL (112.58 mM), Sonication is recommended.
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| 關(guān)鍵字 | 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 |
| 相關(guān)產(chǎn)品 | Imatinib | Gilteritinib | Axitinib | Sorafenib tosylate | Lenvatinib mesylate | Regorafenib | Pazopanib | Nintedanib | Sorafenib | Imatinib Mesylate | Sunitinib | Regorafenib monohydrate |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 抗癌活性化合物庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | 臨床失敗化合物庫(kù) | 激酶抑制劑庫(kù) | 細(xì)胞凋亡化合物庫(kù) | 膜蛋白靶向化合物庫(kù) | 酪氨酸激酶分子庫(kù) | 藥物功能重定位化合物庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |