英文名：PF 06463922

別名： (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

產品名稱： PF 06463922

CAS 登錄號：1454846-35-5, PF 06463922

分子式： C21H19FN6O2

分子量： 406.41

CAS 登錄號： 1454846-35-5

產品簡述 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.

詳細說明 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代產品，在總的ALK抑制劑中劃分到第3代。

現在ALK的用藥方案為克唑替尼--AP26113，CH5424802，LDK378--PF06463922。

3922的作用力為克唑替尼的40倍，是AP26113的6倍。

3922能抑制克唑替尼耐藥之后的9種突變，AP只能抑制劑2種，CH能抑制3種，LDK378能抑制4種，但AP和LDK378是姐妹藥，結構、作用機理基本相同。

3922采用全新的大環(huán)結構，作用機理和效果大幅增加。

3922還可以抑制ros1靶點，其作用力是alk的3倍，是目前ros1的2代藥。

3922應該是目前***廣譜及活性的ALK/ROS抑制劑。