6-氨基-5-[(1R)-1-(2,6-二氯-3-氟苯基)乙氧基]-N-[4-[[(3R,5S)-3,5-二甲基-1-哌嗪基]羰基]苯基]-3-哒嗪甲酰胺
6-氨基-5-[(1R)-1-(2,6-二氯-3-氟苯基)乙氧基]-N-[4-[[(3R,5S)-3,5-二甲基-1-哌嗪基]羰基]苯基]-3-哒嗪甲酰胺
![6-氨基-5-[(1R)-1-(2,6-二氯-3-氟苯基)乙氧基]-N-[4-[[(3R,5S)-3,5-二甲基-1-哌嗪基]羰基]苯基]-3-哒嗪甲酰胺 结构式](https://img.chemicalbook.com/CAS/20180906/GIF/1370651-20-9.gif)
6-氨基-5-[(1R)-1-(2,6-二氯-3-氟苯基)乙氧基]-N-[4-[[(3R,5S)-3,5-二甲基-1-哌嗪基]羰基]苯基]-3-哒嗪甲酰胺 性质
| 储存条件 | Store at -20°C |
|---|---|
| 溶解度 | 溶于二甲基亚砜 |
| 形态 | Solid |
| 颜色 | White to off-white |
| InChIKey | GLYMPHUVMRFTFV-QLFBSQMISA-N |
| SMILES | C1(C(NC2=CC=C(C(N3C[C@H](C)N[C@H](C)C3)=O)C=C2)=O)=NN=C(N)C(O[C@@H](C2=C(Cl)C=CC(F)=C2Cl)C)=C1 |
6-氨基-5-[(1R)-1-(2,6-二氯-3-氟苯基)乙氧基]-N-[4-[[(3R,5S)-3,5-二甲基-1-哌嗪基]羰基]苯基]-3-哒嗪甲酰胺 用途与合成方法
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MET 0.74 nM (IC 50 ) |
The ability of Ensartinib (X-396) to inhibit the growth of different cancer cell lines harboring ALK fusions or point mutations is tested. Ensartinib is potent in H3122 lung cancer cells harboring EML4-ALK E13;A20 (IC 50 : 15nM). Ensartinib is also potent in H2228 lung cancer cells harboring EML4-ALK E6a/b; A20 (IC 50 : 45 nM). Furthermore, X-376 is potent in SUDHL-1 lymphoma cells harboring NPM-ALK (IC 50 : 9 nM). X-376 also inhibits SY5Y neuroblastoma cells harboring ALK F1174L, MKN-45 gastric carcinoma cells harboring MET dependent, HepG2 cells and PC-9 lung cancer cell lines harboring EGFR exon 19 del with IC 50 s of 68 nM, 156 nM, 9.644 μM and 2.989 μM, respectively.
The effects of Ensartinib (X-396) in vivo against H3122 xenografts are examined. A pharmacokinetic study reveals that Ensartinib shows substantial bioavailability and moderate half-lives in vivo. Nude mice harboring H3122 xenografts are treated with Ensartinib at 25mg/kg bid. Ensartinib significantly delays the growth of tumors compared to vehicle alone. In the xenograft experiments, Ensartinib appears well-tolerated in vivo. Mouse weight is unaffected by Ensartinib treatment. Drug-treated mice appear healthy and do not display any signs of compound related toxicity. To further assess potential side effects of Ensartinib, additional systemic toxicity and toxico-kinetic studies are performed in Sprague Dawley (SD) rats. Following 10 days of repeated oral administration of Ensartinib at 20, 40, 80 mg/kg in SD rats, all animals survive to study termination. The no significant toxicity (NST) levels are determined to be 80mg/kg for Ensartinib. At NST levels, Ensartinib achieves an AUC of 66 μM×hr and a C max of 7.19 μM.
