Definition

An orally bioavailable inhibitor of the Rho GTPases Ras-related C3 botulinum toxin substrate (Rac) and cell division control protein 42 homolog (Cdc42), with potential antineoplastic activity. Upon oral administration, Rac/Cdc42 inhibitor MBQ-167 targets, binds to and inhibits the activity of the GTP-binding proteins Rac and Cdc42 that are expressed on certain cancer cells and immunosuppressive immune cells in the tumor microenvironment (TME). This inhibits p21-activated kinase (PAK) and signal transducer and activator of transcription 3 (STAT3) signaling, induces cell-cycle arrest and apoptosis, and inhibits cancer cell proliferation and migration. MBQ-167 also reduces tumor-infiltrating macrophages and myeloid-derived suppressor cells (MDSCs) in the TME, which may abrogate the immunosuppressive nature of the TME. Rac and Cdc42, overexpressed or hyperactivated in various cancers, are homologous, small GTPases that regulate epithelial to mesenchymal transition, cell migration, invasion, and cell cycle progression and metastasis.