Naquotinib
货号：
IN0930
品牌：
Jinpan
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产品简介
| 别名 | ASP8273 |
| CAS | 1448232-80-1 |
| 分子式 | C30H42N8O3 |
| 分子量 | 562.71 |
| 储存条件 | -20℃ |
| 纯度 | ≥98% |
| 单位 | 瓶 |
| 生物活性 | Naquotinib (ASP8273)是一种具有口服活性的、不可逆的、对突变体具有选择性的epidermal growth factor receptor (EGFR)抑制剂，具有潜在的抗肿瘤活性。[1-2] |
| In Vitro | ASP8273是一种不可逆的TKI小分子抑制剂，抑制EGFR突变体包括T97M的激酶活性，而对野生型EGFR的活性有限。在体外酶活性和细胞实验中，ASP8273与EGFR突变体(L858R/T790M)通过半胱氨酸残基共价结合，长效抑制EGFR的磷酸化24小时。在具有上述EGFR突变的NSCLC细胞系中，ASP8273对EGFR突变体的IC50值在8-33 nM 范围间，比对WT EGFR更有效（对WT EGFR的IC50为230 nM）。ASP8273还能通过ERK和Akt抑制信号通路。在对耐其他EGFR TKIs如AZD9291和CO-1686的突变EGFR细胞系张，ASP8273具有活性[1-2]。 |
| In Vivo | 在小鼠肿瘤异种移植研究中，给NCI-H1975 (L858R/T790M), HCC827 (del ex19) and PC-9 (del ex19)异种移植小鼠予以重复的口服给药，ASP8273能以剂量依赖方式诱导肿瘤消退。给药方案并不影响ASP8273的效力。在HCC827和NCI-H1975模型中，10, 30, 100mg/kg的ASP8273可诱导肿瘤消退，而不影响其体重。在NSCLC患者肿瘤源性的异种移植模型（抑制了表达T790M/L858R的LU1868）中，10 mg/kg以上的ASP8273将产生肿瘤生长抑制；另一方面，10 和30mg/kg ASP8273在A431异种移植的模型中没有显著的肿瘤生长抑制作用[1-2]。 |
| SMILES | O=C(C1=NC(CC)=C(O[C@H]2CN(C(C=C)=O)CC2)N=C1NC3=CC=C(N4CCC(N5CCN(C)CC5)CC4)C=C3)N |
| 靶点 | EGFR |
| 动物实验 | ASP8273 selectively inhibited phosphorylation of EGFR and its down-stream signal pathway, ERK and Akt from 10nM in HCC827 and NCI-H1975 while inhibitory effects were only detected at 1000nM in A431.In NCI-H1650 (del ex19), ASP8273 inhibited cell growth with an IC50 value of 70nM while other EGFR-TKIs were only partially effective. ERK and Akt phosphorylation were diminished after ASP8273 treatment at 1000nM, however, other EGFR-TKIs only partially reduced the phosphorylation levels of these proteins. ASP8273 potently enhanced the caspase activity in NCI-H1650 after 24h treatment, which is concordant with signal and cell growth inhibitory effect.[2] |
| 细胞实验 | In HCC827 and NCI-H1975 xenograft models, ASP8273 induced tumor regression at 10, 30 and 100mg/kg without affecting body weight. ASP8273 also produced tumor growth inhibition from 10mg/kg in the NSCLC patient derived tumor xenograft, LU1868 which express T790M/L858R.[2] |
| 数据来源文献 | [1] Sakagami H, et al. Cancer Res. 2014, 74(19 Supplement):1728. [2] Konagai S, et al. Cancer Res. 2015, 75(15 Supplement):2586. |
| 规格 | 5mg |
Naquotinib是一种不可逆的、对突变体具有选择性的epidermal growth factor receptor (EGFR)抑制剂