Rociletinib (CO-1686) 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。
别名:AVL-301, CNX-419
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).
体外实验* | |
---|---|
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® secondary antibodies (LI-COR), washed again, and imaged on an Odyssey Fc (LI-COR). |
浓度 | 2µM |
处理时间 | 72h |
*上述方法来自公开文献,仅供相同目的实验参考。如实验目的、材料、方法不同,请参考其他文献。
体内实验* | |
---|---|
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 |
*上述方法来自公开文献,仅供相同目的实验参考。如实验目的、材料、方法不同,请参考其他文献。
分子量 | 555.55 |
分子式 | C27H28F3N7O3 |
CAS号 | 1374640-70-6 |
溶解性(25°C) | DMSO 50 mg/mL |
储存条件 |
粉末型式 -20°C 3年;4°C 2年 溶于溶剂 -80°C 6个月;-20°C 1个月 |
运输方式 | 冰袋运输,根据产品的不同,可能会有相应调整。 |
*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前,需考虑其在不同溶剂中的溶解度限制。
Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
---|---|---|---|
1 mM | 1.8 mL | 9.0001 mL | 18.0002 mL |
5 mM | 0.36 mL | 1.8 mL | 3.6 mL |
10 mM | 0.18 mL | 0.9 mL | 1.8 mL |
小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 | |
重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km 系数 | 3 | 6 | 12 | 8 | 5 | 20 |
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。
其他相关的EGFR/HER2产品 |
---|
BBT-207
BBT-207是一种可逆的、突变体特异性的 EGFR 抑制剂,具有抗肿瘤活性。 |
VRN-11
VRN-11是一种 EGFR C797S 抑制剂。 |
TRX-221
TRX-221是一种 EGFR C797S 抑制剂。 |
TAS-3351
TAS-3351 是一种表皮生长因子受体 EGFR C797S 抑制剂。 |
Larotinib mesylate hydrate
Larotinib mesylate hydrate 是一种有效的、广谱的、具有口服活性的酪氨酸激酶抑制剂 (TKI),其以 EGFR 为主要靶点,IC50 为 0.6 nM。 |
产品仅供科学研究或药证申报的用途使用,不为任何个人或者非科研性质的其他用途提供服务。
Copyright © 2010-2022 AbMole版权所有 沪ICP备16047849号 沪公网安备 31011502012228号