anti-tumoral activity

BI-1347 is a potent, selective inhibitor of CDK8 cyclinC (IC50: 1 nM). It shows tumor growth inhibition in an in vivo xenograft model.

CV-4-26 (Compound 22) acts as a covalent inhibitor of TEAD. By inhibiting YAP TEAD-driven transcription, it diminishes the expression of CTGF and CYR61. Furthermore, CV-4-26 impedes colony formation in Huh7 and HepG2 cells, inducing cell cycle arrest and apoptosis (apoptosis). This compound demonstrates anti-tumoral activity against hepatocellular carcinoma (HCC) and hepatoblastoma (HB).

Keap1-Nrf2-IN-21 (compound 4d) acts as an inhibitor of glucose metabolism with anti-tumoral properties. It targets the glycolytic pathway by affecting the Keap1-Nrf2 signaling pathway, which in turn suppresses glycolytic activity in cancer cells and inhibits tumor growth. Additionally, Keap1-Nrf2-IN-21 exhibits cytotoxic effects on the HEC1A cell line with an IC50 value of 2.60 μM.

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.