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, an orally active inhibitor of ALK, ROS1, and FAK, demonstrates antitumor efficacy in mouse models of non-small cell lung cancer (NSCLC) [1].

ALK ROS1-IN-4 (example 13) acts as a dual inhibitor targeting both ALK and ROS1 kinase [1].

SIAIS039 is an orally active PROTAC specifically targeting c-ros oncogene 1 (ROS1), demonstrating DC50 values of 154.46 nM, 126.47 nM, and 143.69 nM in HCC78 cells, Ba F3 cells expressing CD74-ROS1 fusion, and Ba F3 cells expressing SDC4-ROS1 fusion, respectively. This compound inhibits proliferation, induces cell cycle arrest, and triggers apoptosis in ROS1-positive cells, while also inhibiting colony formation. In vivo, SIAIS039 exhibits potent anti-tumoral activity against ROS1-driven tumor growth. The composition of SIAIS039 includes the ALK inhibitor Brigatinib, linker EM-12, and VHL E3 ubiquitin ligase ligand.