brigatinib

Brigatinib (AP-26113) is a highly potent and selective inhibitor of ALK.

ALK-IN-1 is a Brigatinib analog and an ALK inhibitor commonly used in anti-tumor research.

SIAIS117, a potent Brigatinib-PROTAC degrader, effectively degrades the ALK G1202R point mutation through its design based on Brigatinib and VHL-1 conjunction. It inhibits the proliferation of SR and H2228 cancer cell lines, demonstrating potential anti-proliferative effects against small cell lung cancer [1].

SIAIS164018, a PROTAC-based ALK and EGFR degrader derived from Brigatinib, exhibits IC50 values of 2.5 nM for ALK and 6.6 nM for ALK G1202R. It significantly hampers cancer cell migration and invasion, induces G1 cell cycle arrest, and triggers apoptosis, demonstrating superior properties compared to Brigatinib [1].

SIAIS164018 hydrochloride is a PROTAC-based degrader targeting ALK and EGFR, exhibiting IC50 values of 2.5 nM for ALK and 6.6 nM for ALK G1202R. It effectively suppresses cancer cell migration and invasion, induces G1 cell cycle arrest, and promotes apoptosis, demonstrating superior properties compared to Brigatinib [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.