Small Molecule Modulation of MEMO1 Protein-Protein Interactions

MEMO1 (mediator of ErbB2-driven cell motility) is upregulated in breast tumors and has been correlated with poor prognosis in patients. As a scaffolding protein that binds to phosphorylated-tyrosine residues on receptors such as estrogen receptor and ErbB2, MEMO1 levels can influence phosphorylation cascades. Using our previously developed fluorescence polarization assay, we have identified small molecules with the ability to disrupt the interactions of MEMO1. We have performed limited structure-activity-relationship studies and computational analyses to investigate the molecular requirements for MEMO1 inhibition. The most promising compounds exhibit slowed migration of breast cancer cell lines (T47D and SKBR3) in a wound-healing assay emulating results obtained from the knockdown of MEMO1 protein. To our knowledge, these are the first small molecules targeting the MEMO1 protein-protein interface and therefore, will be invaluable tools for the investigation of the role of the MEMO1 in breast cancer and other biological contexts.