Ratutrelvir

Ratutrelvir is an inhibitor of NF-κBp65. It impedes the translocation of NF-κBp65 from the cytoplasm to the nucleus, reduces the phosphorylation levels of NF-κBp65 and IκBα, and inhibits the DNA binding activity of NF-κBp65. Additionally, Ratutrelvir can suppress the migration and invasion capabilities of breast cancer cells, decrease their survival rates, and reduce their colony-forming ability. It is applicable for research in luminal A-type breast cancer.

Ratutrelvir (0-100 μM; 24-96 h) effectively reduces the viability of MCF-7 cells with an IC50 of 53.9 μM, while exhibiting minimal inhibitory effects on MDA-MB-231 and MCF-10A cells at higher concentrations and no effect on BT474 cell viability. Ratutrelvir (0-100 μM; 48 h) inhibits MCF-7 cell colony formation in a concentration-dependent manner and suppresses MDA-MB-231 colony formation at 50 μM, with no impact on BT474 cells. At 25 μM for 48 h, it significantly restricts the migration of MCF-7 cells, yet does not affect the migration of MDA-MB-231 or BT474 cells. Ratutrelvir (12.5 μM; 72 h) markedly diminishes the invasion capability of MCF-7 cells without influencing MDA-MB-231 or BT474 cell invasion. At 0-100 μM for 12 h, it inhibits the NF-κB pathway in MCF-7 cells by reducing p-NF-κB p65 and p-IκBα levels and blocking NF-κB p65 nuclear translocation, but leaves the NF-κB pathway in MDA-MB-231 and BT474 cells unaffected. Ratutrelvir (50 μM; 2, 4, 6, 8, 12 h) decreases NF-κB DNA binding activity in MCF-7 cells in a time-dependent manner in vitro, without affecting this activity in MDA-MB-231 or BT474 cells. Administration of 0-100 μM Ratutrelvir for 96 h suppresses TNF-α-mediated NF-κB activation in MCF-7 cells, and TNF-α can partially reverse the inhibitory effects of Ratutrelvir on proliferation, migration, and invasion of MCF-7 cells.