化合物Filanesib TQ0318

Product Introduction
Bioactivity


英文名: Filanesib

描述: Filanesib (ARRY 520) 是一种选择性的驱动蛋白纺锤体蛋白(KSP)的抑制剂(IC50 = 6 nM)，具有强大的抗增殖活性。

细胞实验: Exponentially growing cells (0.4×10^6/mL) are treated with ARRY-520 for up to 48 hours. For combination, HL-60 and HL-60Bcl-2 cells (0.4×10^6/mL) are incubated with ARRY-520, ABT-737, or both for up to 96 hours. DMSO is used as the control agent. Apoptosis is estimated by flow cytometry measurements of phosphatidylserine with the Annexin-V-FLUOS Staining Kit. Membrane integrity is simultaneously assessed by 7-amino-actinomycin D (7-AAD). To measure changes in the mitochondrial membrane potential (MMP), cells are loaded with CMXRos (300 nM) and MitoTracker Green (500 nM) for 1 hour at 37°C. The loss of MMP is then assessed by measuring CMXRos retention while simultaneously adjusting for mitochondrial mass [4].

动物实验: Subcutaneous tumor xenografts are allowed to grow to a volume of 250-350 mm3. The mice are randomized into groups of 3-4 based on tumor size and are given a single dose of ARRY-520 i.p. At various time-points after administration of the drug, the mice are euthanized by CO2 inhalation and the tumors excised and placed in 10% neutral buffered formalin. The formalin-fixed tumors are processed and paraffin-embedded by standard procedures. Spindle morphology is analyzed by staining tumor sections for α-tubulin, and apoptosis is analyzed by TUNEL stain. Monopolar/abnormal spindles and TUNEL positive (apoptotic) cells are counted in three ×40 fields from each sample, analyzed using algorithms developed in software [1].

体外活性: Filanesib在多种耐药细胞系中展示了抗增殖活性，包括HCT-15、NCI/ADR-RES和K562/ADR，其EC50值分别为3.7、14和4.2 nM。Filanesib（10 nM）通过增加组蛋白H3的磷酸化和四个细胞中cyclin B1的积累，阻断有丝分裂并形成典型的KSP抑制效果所表现的单极纺锤体结构[2]。Filanesib（1 nM）在24小时内显著诱导OCI-AML3细胞发生G2M期细胞周期阻滞[4]。

体内活性: Filanesib (10, 15, 20, 30 mg/kg, i.p.) 在UISO-BCA-1异种移植物中表现出活性，且在携带皮下HT-29, HCT-116, MDA-MB-231和A2780异种移植物的小鼠中优于紫杉醇。Filanesib在雄激素受体阴性前列腺癌异种移植模型PC-3中优于多西他赛 [1]。RPMI 8226肿瘤异种移植物对低剂量的Filanesib (12.5 mg/kg, i.p.) 特别敏感 [2]。在SCID小鼠的HL60和MV4-11异种移植物中，Filanesib分别以27 mg/kg和20 mg/kg的浓度显著抑制肿瘤生长 [4]。

存储条件: store at low temperature,keep away from direct sunlightPowder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 90 mg/mL (214 mM)


关键字: Filanesib | ARRY520

相关产品: Ispinesib | SB-743921 hydrochloride | ARRY 520 hydrochloride

相关库: Drug Repurposing Compound Library | Anti-Cancer Compound Library | Anti-Cancer Drug Library | Clinical Compound Library | Bioactive Compounds Library Max | Inhibitor Library | Anti-Cancer Clinical Compound Library | Anti-Cancer Active Compound Library | Bioactive Compound 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