alk/ros1-in-1

ALK ROS1-IN-1 is a potent and selective anti-crizotinib-resistant ALK ROS1 dual inhibitor (IC50s: 0.530 μM and 0.174 μM for ROS1 and ALK enzyme).

PF-06463922 acetate is a potent, selective brain-penetrable inhibitor of both anaplastic lymphoma kinase (ALK) and c-ros Oncogene 1 (ROS1) with strong activity against all known ALK and ROS1 mutants identified in patients with crizotinib-resistant disease. PF-06463922 is in clinical trials for the treatment of non–small cell lung cancer (NSCLC).

APG-2449为口服活性的ALK ROS1 FAK抑制剂，在非小细胞肺癌（NSCLC）的小鼠模型中显示出显著的抗肿瘤效果。

ALK ROS1-IN-4 (示例13) 作为一种针对 ALK 和 ROS1 激酶的双重抑制剂发挥作用。

SIAIS039是一款针对c-ros致癌基因1(ROS1)的口服活性PROTAC,它在HCC78细胞、Ba F3细胞(表达CD74-ROS1融合)以及Ba F3细胞(表达SDC4-ROS1融合)中展现出的DC50分别为154.46 nM、126.47 nM、143.69 nM.该化合物能够抑制ROS1阳性细胞的增殖、诱导细胞周期停滞和细胞凋亡,并有效抑制克隆形成.在动物体内试验中,SIAIS039也显示出了对ROS1驱动型肿瘤生长的明显抑制效果.SIAIS039的组成包括ALK抑制剂Brigatinib、连接子EM-12以及VHL E3泛素连接酶配体。