Description
EHop-016 is an inhibitor of the small Rho GTPases Rac1 and Rac3. It inhibits Rac1 activity in MDA-MB-435 breast cancer cells with an IC
50 value of 1.1 μM in a Rac1 activation assay. At a concentration of 1 μM, EHop-016 inhibits 58% of Rac3 activity, and it inhibits Cdc42 activity but only at higher concentrations (5-10 μM). It also increases Rho GTPase RhoA activity ~1.3-fold at concentrations greater than 2 μM. EHop-016 (2-4 μM) inhibits Rac-regulated functions in MDA-MB-435 cells, including lamellipodia formation and serine/threonine p21-activated kinase 1 (PAK1)-mediated cell migration. In a nude mouse model of breast cancer metastasis, EHop-016 (25 mg/kg) significantly lowers mammary fat pad tumor growth, metastasis, and angiogenesis. It also inhibits mutant receptor tyrosine kinase (KIT)-induced growth in systemic mastocytosis and acute myeloid leukemia (AML) cells (≥2.5 μM).
Uses
EHop-016 has been used as the EHop inhibitor to study signalling diversity during
Chlamydia trachomatis cell entry. It has also been used as a RAC inhibitor.
Biochem/physiol Actions
EHop-016 is a potent and specific inhibitor of Rac1 and Rac3 GTPase activity that inhibits Vav2 interaction with Rac, Rac-activated PAK1, lamellipodia formation, and cell migration. EHop-016 inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation.
