For research use only. Not for therapeutic Use.
Naquotinib (ASP8273) is an orally available, mutant-selective and irreversible EGFR inhibitor; with IC50s of 8-33 nM toward EGFR mutants and 230 nM for EGFR.
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[1]. 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[2].
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[2].
| Catalog Number | I012076 |
| CAS Number | 1448232-80-1 |
| Synonyms | 6-ethyl-3-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]oxypyrazine-2-carboxamide |
| Molecular Formula | C30H42N8O3 |
| Purity | ≥95% |
| InChI | InChI=1S/C30H42N8O3/c1-4-25-30(41-24-12-15-38(20-24)26(39)5-2)34-29(27(33-25)28(31)40)32-21-6-8-22(9-7-21)36-13-10-23(11-14-36)37-18-16-35(3)17-19-37/h5-9,23-24H,2,4,10-20H2,1,3H3,(H2,31,40)(H,32,34)/t24-/m1/s1 |
| InChIKey | QKDCLUARMDUUKN-XMMPIXPASA-N |
| SMILES | 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 |
| Reference | [1]. Sakagami H, et al. ASP8273, a novel mutant-selective irreversible EGFR inhibitor, inhibits growth of non-small cell lung cancer (NSCLC) cells with EGFR activating and T790M resistance mutations. [abstract]. In: Proceedings of the 105th Annual Meeting of t [2]. Konagai S, et al. ASP8273 selectively inhibits mutant EGFR signal pathway and induces tumor shrinkage in EGFR mutated tumor models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Ph |
