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Rociletinib(CO-1686)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Rociletinib(CO-1686)图片
CAS NO:1374640-70-6
包装:5mg, 10mg, 50mg
包装与价格:
包装价格(元)
Free Sample (0.5-1 mg)电议
5mg电议
10mg电议
50mg电议

产品名称
AVL-301, CNX-419
产品介绍

生物活性

Rociletinib (CO-1686,AVL-301)是一种不可逆的,突变选择性的EGFR抑制剂,作用于EGFRL858R/T790M和EGFRWT, Ki分别为21.5 nM和303.3 nM。In NSCLC cells with acquired resistance to CO-1686 in vitro, there was no evidence of additional mutations or amplification of the EGFR gene, but resistant cells exhibited signs of epithelial-mesenchymal transition and demonstrated increased sensitivity to AKT inhibitors. In vivo, Rociletinib (CO-1686) caused dose-dependent and significant tumor growth inhibition in all EGFR-mutant models as well as human EGFRL858R- and EGFRL858R/T790M-expressing transgenic mice. Rociletinib (CO-1686) is approximately 22-fold selective over WT EGFR (kinactt/Ki = (1.12 ± 0.14) x 104 M-1s-1).


化学数据

分子量555.55
分子式C27H28F3N7O3
CAS号1374640-70-6
纯度>99%
溶解性(25°C)DMSO 60 mg/mL
储存和运输条件固体粉末: -20°C 冷藏长期储存
常温运输及临时存放

实验操作 来自于公开的文献,仅供相同实验参考(如实验材料、目的不同,请参考其他文献)

细胞实验
细胞系HCC827 and HCC827-EPR cells
方法Cell signaling analysis of HCC827 and HCC827-EPR HCC827 and HCC827-EPR cells were seeded at 1.5×106 cells per 10 cm2 dish in RPMI 1640, 10 % FBS, 2 mM L-glutamine, and 1% P/S and allowed to adhere overnight. Cells were treated with DMSO, 2 μM CO-1686, or 2 μM erlotinib for 72 hours and lysed. Lysis buffer contained 1X phenylmethanesulfonyl fluoride (Sigma; St. Louis, MO), 1X cell extraction buffer (Life Technologies), 1X protease inhibitor cocktail (Enzo Life Sciences; Farmingdale, NY), 1X phosphatase inhibitor cocktails I and II (EMD Chemicals; Gibbstown, NJ). Total protein concentration was determined using a standard Bradford and measured on a NanoDrop 2000 spectrophotometer (Thermo Scientific; Waltham, MA). Western blotting was performed on cell lysates normalized to 25 μg total protein in loading buffer (LI-COR; Lincoln, NE). Normalized lysates were run on SDS/PAGE and transferred to a nitrocellulose membrane (Life Technologies). The membrane was incubated in Qentix signal enhancement solution (Thermo Scientific), blocked, and incubated overnight at 4°C with primary antibodies (1:1000) from Cell Signaling (Danvers, MA). Membranes were washed, incubated with IRDye(R) secondary antibodies (LI-COR), washed again, and imaged on an Odyssey Fc (LI-COR).
浓度2μM
处理时间72h

动物实验
动物模型EGFR-L858R and EGFR-L858R-T790M;CCSP-rtTA transgenic mouse models
配制resuspended in warmed DMSO:Solutol HS15: PBS (5:15:80; v:v:v)
剂量50 mg/kg BID
给药处理oral gavage

不同实验动物依据体表面积的等效剂量转换表(数据来源于FDA指南)

小鼠大鼠豚鼠仓鼠
重量 (kg)0.020.151.80.40.0810
体表面积 (m2)0.0070.0250.150.050.020.5
Km系数36128520
动物 A (mg/kg) = 动物 B (mg/kg) × 动物 B的Km系数
动物 A的Km系数

例如,依据体表面积折算法,将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量,需要将20 mg/kg 乘以小鼠的Km系数(3),再除以大鼠的Km系数(6),得到化合物用于大鼠的等效剂量为10 mg/kg。


储备液配制

以下数据基于产品分子量,对于特殊产品,请参照COA中的储备液配制条件和说明进行操作。

Concentration / Solvent Volume / Mass1 mg5 mg10 mg
1 mM1.8 mL9.0001 mL18.0002 mL
5 mM0.36 mL1.8 mL3.6 mL
10 mM0.18 mL0.9 mL1.8 mL