hgc

HGC652 is a molecular glue that targets the E3 ubiquitin ligase TRIM21, facilitating the formation of a ternary complex between TRIM21 and NUP98, which induces the degradation of NUP155 and nuclear pore complex proteins, ultimately leading to cell death. HGC652 inhibits the proliferation of various cancer cells, with its antiproliferative activity depending on the expression level of TRIM21.

C-02, a proteolysis-targeting chimera (PROTAC) that combines the hexokinase inhibitor lonidamine with the cereblon ligand thalidomide, effectively induces the degradation of hexokinase 2 in 786-O and PANC-1 cells at a concentration of 20 µM. This compound exhibits cytotoxicity to a range of cancer cells, including 786-O, 4T1, PANC-1, HGC-27, and MCF-7, with IC50 values of 34.07 µM, 5.08 µM, 31.53 µM, 6.11 µM, and 21.65 µM, respectively. Additionally, at 20 µM, C-02 diminishes both the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in 4T1 cells, suggesting a suppression of glycolysis and mitochondrial damage. In vivo studies reveal that at a dosage of 50 mg/kg, C-02 not only reduces tumor volume but also promotes intratumoral cytokine accumulation and triggers pyroptosis in a 4T1 murine mammary carcinoma model.