化合物CYC065 TQ0053

Product Introduction
Bioactivity


英文名: Fadraciclib

描述: Fadraciclib (CYC065) 是一种口服有效的 ATP 竞争性的CDK2/CDK9激酶抑制剂，IC50分别为 5 和 26 nM。

细胞实验: Briefly, tumour cells are plated in six-well plates and treated with a titration of CYC065 concentrations (i.e., ranging from 100 to 500?nM). After 72?h, cells are harvested, washed and stained with propidium iodide (PI; 5?μg/mL) for flow cytometric counts. The percentage of viable cells is then normalized considering the vehicle-treated cells as 100% viable. Half-maximal inhibitory concentration values are determined using GraphPad Prism5 version 6. For drug combination studies, USC-ARK-1 and USC-ARK-2 cell lines are incubated with the combination of Taselisib and CYC065 at multiple paired concentrations including the IC50, the IC50/2 and the IC50*2 of each cell line to the corresponding drug (i.e., 10?nM of Taselisib and 198?nM of CYC065 for USC-ARK-1 and 50?nM of Taselisib and 62.5?nM of CYC065 for USC-ARK-2). Synergism is assessed by the combination index (CI). CI values <1 define a synergistic activity of the combination treatment. The CI values are calculated using the CompuSyn software [1].

动物实验: Briefly, 5-7-week-old SCID mice are injected into the subcutaneous region with USC cells. A minimum of five animals per group are used. Treatments are administrated by oral gavage starting 1 week after tumor implantation when the size of the tumor is 0.125-0.150?cm3. Uterine serous carcinoma-ARK-2-derived xenografts are divided into two groups: one group of animal receive the vehicle, whereas the experimental group receives CYC065 (22.5?mg/kg daily for 3 weeks). Uterine serous carcinoma-ARK-1-derived xenografts are instead divided into four groups: one group receive the vehicle (0.5% methylcellulose-0.2% Tween-80), one group receive CYC065 (22.5?mg/kg daily for 3 weeks), one group receive Taselisib (10 mg/kg daily, 5 days per week per 3 weeks) and the last group receive the combination of CYC065 and Taselisib. The size of the tumor at the initiation of treatment is 0.125-0.150?cm3. Mouse weight and tumor size is recorded two times a week for the entire experimental period. Tumor volume is calculated.

体外活性: CYC065通过阻碍细胞在细胞周期G1阶段的活动，并特异性抑制在环形蛋白E1 (CCNE1) 过表达的子宫浆液性癌症(USCs)中的细胞生长。与低CCNE1表达的细胞系相比，高CCNE1 mRNA及蛋白水平的USC细胞系对CYC065的治疗表现出更高的敏感性（IC50: 平均±标准差=124.1±57.8nM 对CCNE1过表达的USC细胞系 vs 415±117.5nM 对CCNE1低表达者；P=0.0003）。重要的是，低浓度的CYC065（即，100nM）仅在CCNE1过表达的USC细胞系中引起细胞周期G1阶段的停滞[1]。

体内活性: USC-ARK-2衍生的异种移植物每日使用CYC065 (22.5 mg/kg)治疗共3周。肿瘤大小与小鼠体重每周记录两次。CYC065的日常给药显著减缓了与对照组相比的肿瘤生长（治疗第9天起，P=0.012）。整个治疗期间未报告有显著的体重减轻[1]。

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

溶解度: DMSO : 100 mg/mL (251.56 mM)


关键字: Cyclin dependent kinase | Inhibitor | Fadraciclib | CYC 065 | CYC-065 | inhibit | CDK

相关产品: 2-Chloropyrazine | RGB-286638 free base | FN-1501-propionic acid | TAK-901 | GW779439X | PROTAC CDK9/CycT1 Degrader-2 | PF07104091 | XPW1 | Trilaciclib | AS-0141

相关库: Drug Repurposing Compound Library | Cell Cycle Compound Library | Anti-Cancer Drug Library | Anti-Cancer Clinical Compound Library | Kinase Inhibitor Library | Inhibitor Library | Anti-Cancer Active Compound Library | Hematonosis Compound Library | Orally Active Compound Library | NO PAINS 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