英文名：PF 06463922

别名： (10R)-7-Amino-12-fluoro-10,15,16,17-tetrahydro-2,10,16-trimethyl-15-oxo-2H-4,8-methenopyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile

产品名称： PF 06463922

CAS 登录号：1454846-35-5, PF 06463922

分子式： C21H19FN6O2

分子量： 406.41

CAS 登录号： 1454846-35-5

产品简述 PF-06463922 is a novel, orally available, CNS-penetrant, ATP-competitive inhibitor of ALK/ROS1 with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively.

详细说明 PF-06463922 demonstrates significant cell activity against ALK and a large set of ALK clinical mutations with IC50 ranging from 0.2 nM-77 nM. PF-06463922 exhibited subnanomolar cellular potency against oncogenic ROS1 fusions and inhibited the crizotinib-refractory ROS1(G2032R) mutation and the ROS1(G2026M) gatekeeper mutation. Compared with crizotinib and the second-generation ALK/ROS1 inhibitors ceritinib and alectinib, PF-06463922 showed significantly improved inhibitory activity against ROS1 kinase. in vivo: PF-06463922 showed marked antitumor activity in tumor models expressing FIG-ROS1, CD74-ROS1, and the CD74-ROS1(G2032R) mutation. Furthermore, PF-06463922 demonstrated antitumor activity in a genetically engineered mouse model of FIG-ROS1 glioblastoma.

PF06463622是克唑替尼2代产品，在总的ALK抑制剂中划分到第3代。

现在ALK的用药方案为克唑替尼--AP26113，CH5424802，LDK378--PF06463922。

3922的作用力为克唑替尼的40倍，是AP26113的6倍。

3922能抑制克唑替尼耐药之后的9种突变，AP只能抑制剂2种，CH能抑制3种，LDK378能抑制4种，但AP和LDK378是姐妹药，结构、作用机理基本相同。

3922采用全新的大环结构，作用机理和效果大幅增加。

3922还可以抑制ros1靶点，其作用力是alk的3倍，是目前ros1的2代药。

3922应该是目前***广谱及活性的ALK/ROS抑制剂。