IGGi-11me, a prodrug that can permeate membranes, is derived from IGGi-11, the inaugural inhibitor targeting the noncanonical activation of heterotrimeric G-protein signaling. By binding to G-protein α-subunits (Gαi), IGGi-11 specifically disrupts their interaction with GIV/Girdin, thereby obstructing noncanonical G-protein signaling in tumor cells and hindering the proinvasive characteristics of metastatic cancer cells.