新药CO-1686研究报告（摘选）
Results: In vitro and in vivo pharmacology studies were conducted to evaluate CO-1686 potency in four EGFR
mutations common in NSCLC patients: L858R, delE746-A750, L858R/T790M and delE746-A750/T790M. CO-1686
was shown to be active against all four EGFR mutants. Effects of CO-1686 on cell proliferation and EGFR signaling
were evaluated in HCC827 cells (delE746-A750) and its erlotinib-resistant clone, HCC827-EPR harboring the second
site mutation T790M (delE746-A750/T790M). CO-1686 inhibited cell proliferation in both cell lines equally. In mouse
xenograft studies, oral dosing of CO-1686 in double mutant (L858R/T790M) and in single mutant (delE746-A750)
models caused tumor shrinkage as a single agent in a dose-dependent manner. Different dosing schedules were
explored.
Conclusions: Our results establish CO-1686 as a potent, mutant-selective EGFR inhibitor with excellent in vivo
activity in mice bearing tumors with activating EGFR mutations as well as the resistance mutation T790M. These data
suggest that treatment with CO-1686 as a single agent may overcome T790M-mediated drug resistance in NSCLC.
Initially, clinical development will focus on NSCLC patients with mutant EGFR.
keenman 发表于 2012-12-4 09:23 static/image/common/back.gif
这个帖子讨论的内容非常好，看来能用化疗或者抗血管生成药在易瑞沙和特罗凯之间缓冲，是有理论依据的
请问有哪些抗血管生成药？谢谢
米,你研究wz4002好深入啊,尽管上面的图和英文我什么也看不明白,我真心祝愿向你致敬!希望像你这样的前行者能给我们带来更多的福音!
真是给患者带来一个好消息。感谢！
天空的颜色 发表于 2012-12-18 16:40 static/image/common/back.gif
请问有哪些抗血管生成药？谢谢
目前我所了解的抗血管生成药，使用较多的有凡德他尼、阿西替尼，另外还有最新的Tivozanib药
谢谢“又一个五年”，刚刚在Q上向你学了很多，也更加迷惑了。唉
标记个，母亲易耐药中
我也希望早一点试用WZ4002！！！
又一个五年分析的很好，我觉得像2992还有别的针对野生型EGFR或者VEGF的药，大家要慎用，人体是很复杂的，你如果阻止了这些通路，他会很快找到新的通路绕过原有通路，比如说高表达这些受体，就如同筑坝防水患，坝越筑越高，水也越来越高，危险也越来越大，所以特异性高的药，如WZ4002和CO1686是真正的出路。大家群策群力应用这两个药才是正道。
谁有时间可以整理一下，药物对野生型和突变型靶点特异性差别。我有印象易瑞沙，特罗凯都是对突变的EGFR结合比对野生型高100倍左右，WZ4002， CO1686 也是这样，只是这两个药更是针对易特耐药后的突变，动物实验也没有见到很强的副作用，这种小分子化合物针对突变的结构干扰体内的正常功能的可能应该比较小。大家有试非正版的希望能尽快通知效果到班上，这应该是耐药的出路。 另外，像EGFR和VEGF野生型抑制剂，单抗，古巴疫苗等肯定不是长久或最终出路。