Linifanib
作者：齊岳
發布時間：2023-08-22
09:28:19
點擊數：
產品名稱：Linifanib
產品描述：
| 產品描述 | Linifanib (ABT-869) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR (IC50: 4 nM), CSF-1R (IC50: 3 nM), Flt-1/3 (IC50: 3/4 nM) and PDGFRβ (IC50: 66 nM). Linifanib may exhibit potent antiproliferative and apoptotic effects on tumor cells whose proliferation is dependent on mutant kinases, such as FMS-related tyrosine kinase receptor-3 (FLT3). |
| 靶點活性 | FLT3:4 nM, PDGFRβ:66 nM, Flt1:3 nM, CSF-1R:3 nM, KDR:4 nM |
| 體外活性 | 在肺組織中,Linifanib（0.3 mg/kg）使血管內皮生長因子受體磷酸化被完全抑制.在角膜上,每天兩次 Linifanib（7.5/15 mg/kg）顯著抑制重組堿性成纖維細胞生長因子-和血管內皮生長因子誘導的血管生成.在MDA-231移植瘤中,Linifanib（12.5 mg/kg,2次/天）可降低微脈管密度.Linifanib也抑制水腫反應（ED50：0.5 mg/kg）.作用于移植瘤模型,包括HT1080, H526, MX-1和DLD-1時,Linifanib抑制生長（ED75：4.5-12 mg/kg）.作用于在HT1080纖維肉瘤模型中,Linifanib的Cmax和AUC24小時分別為0.4 μg/mL和2.7 μg·hour/mL. |
| 體內活性 | ABT-869對血管內皮生長因子-刺激的人臍動脈內皮細胞增殖有抑制作用（IC50：0.2 nM）。在激酶實驗中,Linifanib抑制Kit（IC50：14 nM）、PDGFRβ（IC50：66 nM）和Flt4（IC50：190 nM）。Linifanib也抑制細胞水平配體誘導的KDR（IC50：2 nM）、PDGFR-β（IC50：2 nM）、KIT（IC50：31 nM）和CSF-1R（IC50：10 nM）磷酸化,血清蛋白可影響該效力。在Ba/F3 FLT3 ITD細胞中,Linifanib（10 nM）降低Akt在Ser473位點磷酸化及GSK3β在Ser9位點磷酸化。然而,ABT-869幾乎不影響不受血管內皮生長因子或血小板衍生因子誘導的細胞,除MV4-11白血病細胞(具有組成型活性形式Flt3,IC50：4 nM)。Linifanib可與CSF-1R的ATP結合位點結合（Ki：3 nM）。 |
| 激酶實驗 | Kinase assays: Potencies (IC50 values) are determined by assays of active kinase domains cloned and expressed in baculovirus using the FastBacbaculovirus expression system or obtained commercially. For tyrosine kinase assays, a biotinylated peptide substrate containing a single tyrosine is used with 1 mM ATP, anEu-cryptate–labeled anti-phosphotyrosine antibody (PT66), and Strepavidin-APC in a homogeneous time-resolved fluorescence assay. Serine/threonine kinases are assayed using 5 μM ATP, [33P]ATP, and a biotinylated peptide substrate with peptide capture and incorporation of 33P determined using a SA-Flashplate. Linifanib is assayed at multiple concentrations prepared by serial dilution of a DMSO stock solution of Linifanib. The concentration resulting in 50% inhibition of activity is calculated using nonlinear regression analysis of the concentration response data. |
| 細胞實驗 | Cells are seeded into 96-well plates at 2.5 × 103 per well and incubated with serum-free medium for 24 hours. Linifanib and VEGF (final, 10 ng/mL) are added and incubated for 72 hours in serum-free medium. For carcinoma cell lines, 3 × 103 cells/well are plated overnight in full growth medium. Linifanib is added to the cells in full growth medium and incubated for 72 hours. For leukemia cells, generally 5 × 104 per well are plated in full growth medium, Linifanib is added, and incubated for 72 hours. The effects on proliferation are determined by addition of Alamar Blue (final solution, 10%), incubation for 4 hours at 37 °C in a CO2 incubator and analysis in a fluorescence plate reader (544 nm, excitation: 590 nm, emission(Only for Reference) |
| 別名 | RG3635, ABT-869, AL-39324 |
| 分子量 | 375.407 |
| 分子式 | C21H18FN5O |
| CAS No. | 796967-16-3 |
存儲
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
Ethanol: <1 mg/mL
DMSO: 70 mg/mL (186.5 mM)
H2O: <1 mg/mL
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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