Naquotinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Naquotinib (ASP-8273) 是一种有效的、不可逆的、突变选择性的 EGFR 抑制剂。

Naquotinib (ASP-8273) is a potent, irreversible, mutant-selective inhibitor of EGFR (IC50=8-33 nM for (L858R, exon 19 deletion, L858R/T790M, and del19/T790M)); more potently than that of WT EGFR (IC50= 230 nM); shows activity in mutant EGFR cell line which is resistant to other EGFR TKIs including AZD9291 and CO-1686.Lung Cancer Phase 1 Discontinued.

In assays using endogenously EGFR-dependent cells, Naquotinib inhibits the growth of PC-9(del ex19), HCC827(del ex19), NCI-H1975(del ex19/T790M) and PC-9ER(del ex19/T790M) with IC50s of 8-33 nM. Naquotinib selectively inhibits phosphorylation of EGFR and its down-stream signal pathway, ERK and Akt from 10nM in HCC827 and NCI-H1975 while inhibitory effects are only detected at 1000nM in A431.In NCI-H1650 (del ex19), Naquotinib inhibits cell growth with an IC50 value of 70nM while other EGFR-TKIs are only partially effective.

Oral Naquotinib treatment dose dependently induces tumor regression in NCI-H1975 (L858R/T790M), HCC827 (del ex19) and PC-9 (del ex19) xenograft models. Dosing schedules does not affect the efficacy of Naquotinib. In an NCI-H1975 xenograft model, complete regression of tumor is achieved after 14-days of Naquotinib treatment. Complete regression is maintained in 50% of mice more than 85 days after cessation of Naquotinib treatment.

ASP8273

Angiogenesis

EGFR

EGFR

Cancer

Lung Cancer

1448232-80-1

562.7063

C30H42N8O3

>98% (HPLC)

DMSO

CCC1=C(N=C(C(=N1)C(=O)N)NC2=CC=C(C=C2)N3CCC(CC3)N4CCN(CC4)C)OC5CCN(C5)C(=O)C=C

2-Pyrazinecarboxamide, 6-ethyl-3-[[4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]amino]-5-[[(3R)-1-(1-oxo-2-propen-1-yl)-3-pyrrolidinyl]oxy]-

(-20℃)

With Ice Pack

≥ 2 years