MBQ-167 is a dual inhibitor of Rac/Cdc42 (IC50s: 103 nM for Rac 1/2/3 and 78 nM for Cdc42 in MDA-MB-231 cells, respectively).

CDC42:78 nM, Ras1/2/3:103 nM

MBQ-167 causes this phenotype in multiple mesenchymal cancer cell types including GFP-HER2-BM, MDA-MB-468, and Hs578t human breast cancer cells, as well as Mia-PaCa-2 pancreatic cancer cells, SKOV3 ovarian cancer cells, AGS and NCI-N87 gastric cancer cells, and SH-SY5Y neuroblastoma cells. MBQ-167 (≥100 nM) causes a loss of polarity in metastatic breast cancer cells. MBQ-167(500 nM; 24 h)treatment, results in ~95% cell rounding and detachment from the substratum in metastatic MDA-MB-231 cells. At earlier times (6h), MBQ-167(250 or 500 nM)treatment, induce an inhibition in Rac activity in the attached cell population, while the detached population demonstrates a ~40-50% inhibition. The attached population of MDA-MB-231 cells demonstrate a ~25% decrease in Rac activation while the detached cells are more responsive with a ~75% decrease following treatment with 250 nM MBQ-167 for 24 h .

Mice treated with MBQ-167 exhibited comparable doubling times for the treatments (10 and 11 days), and demonstrated a statistically significant decrease in tumor growth. Upon sacrifice, a dosage of 1.0 mg/kg body weight (BW) with MBQ-167 led to an approximate 80% reduction in tumor size, while a higher dose of 10 mg/kg BW achieved an approximate 95% reduction. In comparison, EHop-016 at a 10 mg/kg BW dosage resulted in about a 40% reduction in tumor growth, making MBQ-167 ten times more effective than EHop-016.