1365267-27-1
基本信息
恩沙替尼(X-376)
恩沙替尼(X 396)
ALK抑制劑(ENSARTINIB)
X-376
CS-1720
Ensartinib
(R)-6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-N-(4-(4-methylpiperazine-1-carbonyl)phenyl)pyridazine-3-carboxamide
6-amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-[4-(4-methylpiperazine-1-carbonyl)phenyl]pyridazine-3-carboxamide
6-Amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-[4-[(4-methyl-1-piperazinyl)carbonyl]phenyl]-3-pyridazinecarboxamide
3-Pyridazinecarboxamide, 6-amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-[4-[(4-methyl-1-piperazinyl)carbonyl]phenyl]-
物理化學性質(zhì)
常見問題列表
恩沙替尼治療較常見的副作用包括皮疹、瘙癢、水腫、貧血等,大多數(shù)為1-2級,程度輕微,發(fā)生率最高的3級或以上明顯副作用為皮疹(6%)和顏面部水腫(4%)。恩沙替尼治療過程中較常見的實驗室檢查結果異常,包括肝酶兩項、γ-谷氨酰轉(zhuǎn)肽酶、堿性磷酸酶、血清淀粉酶和血肌酐升高。
Target | Value |
ALK
() |
The ability of X-376 to inhibit the growth of different cancer cell lines harboring ALK fusions or point mutations is tested. X-376 is potent in H3122 lung cancer cells harboring EML4-ALK E13;A20 (IC 50 : 77 nM). X-376 is also potent in H2228 lung cancer cells harboring EML4-ALK E6a/b; A20 (IC 50 : 57 nM). Furthermore, X-376 is potent in SUDHL-1 lymphoma cells harboring NPM-ALK (IC 50 : 32 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 142 nM, 150 nM, 15.137 μM and 3.062 μM, respectively.
The effects of X-376 in vivo against H3122 xenografts are examined. A pharmacokinetic study reveals that X-376 shows substantial bioavailability and moderate half-lives in vivo. Nude mice harboring H3122 xenografts are treated with X-376 at 50 mg/kg bid. X-376 significantly delays the growth of tumors compared to vehicle alone. In the xenograft experiments, X-376 appears well-tolerated in vivo. Mouse weight is unaffected by X-376 treatment. Drug-treated mice appear healthy and do not display any signs of compound related toxicity. To further assess potential side effects of X-376, additional systemic toxicity and toxico-kinetic studies are performed in Sprague Dawley (SD) rats. Following 10 days of repeated oral administration of X-376 at 25, 50, 100 mg/kg in SD rats, all animals survive to study termination. The no significant toxicity (NST) levels are determined to be 50 mg/kg for X-376. At NST levels, X-376 achieves an AUC of 41 μM×hr and a C max of 5.04 μM.