| CAS |
No.1374640-70-6 |
| 英文名称 |
CO-1686 |
| 别名 |
;CNX-419;AVL-301; |
| 分子式 |
C27H28F3N7O3 |
| 分子量 |
555.55 |
| 溶解性 |
Soluble in DMSO(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD26793864 |
| SMILES |
CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)NC4=CC(=CC=C4)NC(=O)C=C)C(F)(F)F)OC |
| InChIKey |
HUFOZJXAKZVRNJ-UHFFFAOYSA-N |
| InChI |
InChI=1S/C27H28F3N7O3/c1-4-24(39)32-18-6-5-7-19(14-18)33-25-21(27(28，29)30)16-31-26(35-25)34-22-9-8-20(15-23(22)40-3)37-12-10-36(11-13-37)17(2)38/h4-9，14-16H，1，10-13H2，2-3H3，(H，32，39)(H2，31，33，34，35) |
| PubChem CID |
57335384 |
| 靶点 |
EGFR |
| 通路 |
Angiogenesis;Protein Tyrosine Kinase/RTK |
| 背景说明 |
CO-1686是一种不可逆的EGFR。 |
| 生物活性 |
Rociletinib (CO-1686) is an orally delivered kinase inhibitor that specifically targets the mutant forms of EGFR including T790M， and the Ki values for EGFRL858R/T790M and EGFRWT are 21.5 nM and 303.3 nM， respectively.[1] |
| IC50 |
EGFRL858R/T790M 21.5 nM (Ki) EGFRT790M 303.3 nM (Ki)[1] |
| In Vitro |
Rociletinib (CO-1686) (0.1 μM) 有效且不可逆地抑制 EGFR，并抑制 23 个靶标中超过 50% 的靶标。Rociletinib 有效且选择性地抑制表达突变型 EGFR 的 NSCLC 细胞的生长并诱导细胞凋亡。Rociletinib 耐药的 NSCLC 细胞系对 AKT 抑制敏感[1]。 |
| In Vivo |
Rociletinib (CO-1686) (100 mg/kg/天，口服) 在 NSCLC EGFR 突变体异种移植模型中表现出抗肿瘤活性。Rociletinib (CO-1686) (50 mg/kg bid，po) 在表达人 EGFR-L858R 和 EGFR-L858R-T790M 的转基因小鼠中表现出抗肿瘤活性[1]。 |
| 细胞实验 |
Cells are seeded at 3，000 cells/well in growth media supplemented with 5% FBS， 2 mM L-glutamine， and 1 % P/S， allowed to adhere overnight， and treated with a dilution series of test compound (Rociletinib) for 72 hr. Cell viability is determined by CellTiter Glo and results are represented as background-subtracted relative light units normalized to a DMSO-treated control. Growth inhibition (GI50) values are determined by GraphPad Prism 5.04. Combination index (CI) data is generated using CalcuSyn. |
| 动物实验 |
Briefly， NCr nu/nu mice are sub-cutaneously implanted with 1×107?tumor cells in 50% Matrigel (injection volume of 0.2 mL/mouse). Once tumors reached 100-200 mm3， Animals are dosed with compounds (Rociletinib) as outlined (N=10 animals/gp). Briefly， LUM1686 PDX tumor fragments， harvested from donor mice， are inoculated into BALB/c nude mice. Administration of test compounds (Rociletinib (CO-1686)) is initiated at a mean tumor size of approximately 160 mm3. Tumor growth is monitored over time to determine tumor growth inhibition of the experimental agent vs. vehicle. The endpoint of the experiment is a mean tumor volume (MTV) in control group of 2000 mm3. Percent TGI is defined as the difference between the MTV of the designated control group and the MTV of the drug-treated group， expressed as a percentage of the MTV of the designated control group. Data is presented as mean±standard error of the mean (SEM). |
| 数据来源文献 |
[1]. Walter AO， et al. Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Cancer Discov. 2013 Sep 25. |
| 规格 |
5mg 10mg 50mg 100mg |
| 单位 |
瓶 |
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