The Cellular Effects of An Allosteric HER2 Homodimerization Inhibitor

The Human Epidermal growth factor Receptor-2 (HER2) involved in cancer signaling is a clinically validated target overexpressed in aggressive types of breast cancer. Its activity is mediated through a critical dimerization step necessary to initiate downstream signaling that controls cellular growth and division. We discovered a hit compound, UTF-H20323, predicted to inhibit HER2 allosterically by halting dimerization. Cellular studies were conducted using SK-Br-3 cell line overexpressing HER2 to assess the compound's efficacy. The expression level and localization of HER2 receptors as well as the level of cellular apoptosis were studied using immunofluorescence imaging. A decrease in HER2 expression level was noticed after 24 hours incubation with UTF-H20323 coupled with receptor internalization. Immunofluorescence staining revealed a qualitative increase in apoptotic cells equivalent to the clinically used inhibitor lapatinib. The results confirm the cellular activity of the discovered hit leading to growth inhibition of cancerous cells.