IGGi-11me is a specific, cell-active small molecule inhibitor of GIV-dependent G-protein cell signaling, binds to G-protein α-subunits, specifically disrupts their engagement with GIV/Girdin.
IGGi-11me was converted to IGGi-11 (Cat# PC-20013) by esterases present in the cytosol of MDA-MB-231 cells.
IGGi-11me specifically inhibits GIV-dependent cancer cell signaling reduced the phosphorylation of Akt at S473 (pAkt) upon EGF stimulation in MDA-MB-231 (IC50=16 uM) and HeLa cells, but not in GIV-depleted cells.
IGGi-11me does not affect GIV-independent G-protein cell signaling.
IGGi-11me specifically inhibits GIV-dependent tumor cell migration, IGGi-11me was approximately four times more potent inhibiting the migration of MDA-MB-231 cells (GIVHigh) than of MCF-7 cells (GIVLow).
IGGi-11me inhibits growth of MDA-MB-231 breast cancer invasive cells, but not of non-transformed MCF-10A cells.
IGGi-11me inhibits MDA-MB-231 cell tumor growth and metastatic invasion in NCr nu/nu athymic nude mice.