Information Naquotinib (ASP8273) is an orally available, irreversible, mutant-selective,epidermal growth factor receptor (EGFR)inhibitor, with potential antineoplastic activity. Targets mutant EGFR In vitro ASP8273 is a small-molecule irreversible TKI inhibitor that inhibits the kinase activity of EGFR mutations including T790M, with limited activity against EGFR wild-type (WT) NSCLC. In the in vitro enzymatic and cell-based assays, ASP8273 is evaluated against EGFR mutants (L858R, exon 19 deletion, L858R/T790M, and del19/T790M) and WT EGFR. ASP8273 is found by mass spectrometry to covalently bind to a mutant EGFR (L858R/T790M) via cysteine residue 797 in the kinase domain of EGFR with long-lasting inhibition of EGFR phosphorylation for 24 h. In the NSCLC cell lines harboring the above EGFR mutations, ASP8273 has IC50 values of 8-33 nM toward EGFR mutants, more potently than that of WT EGFR (IC50 value of 230 nM). ASP8273 is further shown to suppress the signaling pathway through ERK and Akt. ASP8273 even shows activity in mutant EGFR cell line which is resistant to other EGFR TKIs including AZD9291 and CO-1686. In vivo In mouse xenograft studies, ASP8273 induces tumor regression in NCI-H1975 (L858R/T790M), HCC827 (del ex19) and PC-9 (del ex19) xenograft models by repeated oral dosing in a dose-dependent manner. Dosing schedules do not affect the efficacy of ASP8273. In HCC827 and NCI-H1975 xenograft models, ASP8273 induces tumor regression at 10, 30 and 100mg/kg without affecting body weight. ASP8273 also produces tumor growth inhibition from 10mg/kg in the NSCLC patient derived tumor xenograft, LU1868 which express T790M/L858R. On the other hand, ASP8273 does not produce significant tumor growth inhibition at 10 and 30mg/kg in A431 xenograft model.
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Naquotinib(ASP8273)
CAS number：1448232-80-1 molecular formula：C30H42N8O3
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| Chinese alias | 那可替尼(ASP8273) | ||
| English alias | D10958 | NAQUOTINIB [INN] | CCG-270060 | ASP8273 | ASP-8273 | VS-12093 | 6-ethyl-3-[[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]amino]-5-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]oxy-pyrazin | NSC793322 | NSC-793322 | YHC23280 | A14408 | Naquotinib | AK | ||
| CAS number | 1448232-80-1 | molecular formula | C30H42N8O3 |
| molecular weight | 562.71 g/mol | Exact mass | - |
| PSA | 120.000 Ų | logp | 2.756 |
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