AZD3229 Tosylate is a potent pan-KIT mutant inhibitor for the treatment of gastrointestinal stromal tumors.
纯度
98%
储存/保存方法
Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.
基本信息
可溶性/溶解性
DMSO : ≥ 100 mg/mL (153.44 mM)
生物活性
靶点
KIT.
In vitro(体外研究)
AZD3229 is a potent, pan-KIT mutant inhibitor with potent single digit nM growth inhibition against a diverse panel of mutant KIT driven Ba/F3 cell lines (GI50=1-50 nM). AZD3229 demonstrates potent single digit nM growth inhibition across a broad cell panel, with good margin to KDR-driven effects. Selectivity over KDR can be rationalised predominantly by the interaction of water molecules with the protein and ligand in the active site and its kinome selectivity is similar to the best of the approved GIST agents.
In vivo(体内研究)
AZD3229 is a potent, pan-KIT mutant inhibitor with potent single digit nM growth inhibition against a diverse panel of mutant KIT driven Ba/F3 cell lines (GI50=1-50 nM). AZD3229 demonstrates potent single digit nM growth inhibition across a broad cell panel, with good margin to KDR-driven effects. Selectivity over KDR can be rationalised predominantly by the interaction of water molecules with the protein and ligand in the active site and its kinome selectivity is similar to the best of the approved GIST agents.
小鼠[2]对于剂量反应实验，给予携带06-0606和10-0505异种移植物的小鼠4次口服索拉非尼（10,30,50和100mg/kg每日），持续12天。每个治疗组由五只小鼠组成。为了研究索拉非尼的抗肿瘤作用，每天口服给予患有肿瘤的小鼠50mg/kg索拉非尼，持续12天。每个处理组由14只动物组成，每个实验重复至少两次。肿瘤植入后第7天开始治疗。到这时，HCC异种移植物达到约100mm 3的大小。为了研究雷帕霉素和索拉非尼对10-0505异种移植物生长的影响，给患有肿瘤的小鼠（每组14只）口服200μL载体，或50mg/kg索拉非尼，或1mg/kg雷帕霉素，或指示天或雷帕霉素加索拉非尼。通过游标卡尺测量肿瘤的长度和宽度，每周至少监测肿瘤生长两次。肿瘤体积计算如下：[长×宽2×π/ 6]。在研究结束时，用体重杀死小鼠并记录肿瘤重量，收集肿瘤用于分析。大鼠[3]在该研究中，使用100至120g雄性白化病大鼠。在适应期后，将大鼠称重并随机分成三组：第1组（正常对照组; n = 10）每天给予载体8周。第2组（DENA组; n = 15）接受ip单剂量的200mg/kg DENA。第3组（索拉非尼组; n = 12）在DENA ip注射后6周，以10mg/kg的剂量口服给予索拉非尼，持续2周。在实验结束时（8周），将大鼠称重，用乙醚麻醉并杀死，解剖它们的肝脏。将新鲜肝脏用冰冷的盐水洗涤两次，用干净的纸巾擦干，并称重。肝脏指数计算为肝脏重量（g）/最终体重（g）×100。将肝脏分成五部分：一部分保存在10％福尔马林中用于组织病理学检查，另一部分立即在液氮中冷冻并储存在-80℃。
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