SIAIS039

Description

SIAIS039 is an orally active c-ros oncogene 1 ROS1 -specific PROTAC with DC50s of 154.46 nM, 126.47 nM, 143.69 nM for HCC78 cells, Ba/F3 expressing the CD74-ROS1 fusion and Ba/F3 expressing the SDC4-ROS1 fusion, respectively. SIAIS039 suppresses cell proliferation, induces cell cycle arrest and apoptosis, and inhibits clonogenicity against ROS1-positive cells. SIAIS039 demonstrates anti-tumour effects against ROS1-driven tumor growth vivo. SIAIS039 is composed of the ALK inhibitor Brigatinib HY-12857 , a linker EM-12 HY-138793 , and a VHL ligand E3 ubiquitin ligase 1-Butyne Red: Brigatinib; Blue: VHL ligand; Black: linker .