Rac1-IN-5 is a selective, reversible inhibitor of the RAC1 protein with a dissociation constant (KD) of 30 nM. It competes specifically with guanine nucleotides for binding to RAC proteins, effectively blocking RAC1 activity and RAC1-dependent cellular functions. In vivo, Rac1-IN-5 exhibits anti-tumor metastasis effects and can improve survival rates. This compound is applicable for research on aggressive cancers such as triple-negative breast cancer and colon cancer.

Rac1-IN-5 (Compound A41) at 10 μM for 1 hour inhibits RAC1 activation and its dependent functions in EGF-stimulated NIH/3T3 fibroblasts. Additionally, Rac1-IN-5 at 10 μM decreases the activity of RAC P29S and RAC1b in NIH-3T3 fibroblasts expressing RAC wild-type (RAC1 WT) or RAC1 mutants (RAC1 P29S and RAC1b). In the concentration range of 0.01-10 μM, Rac1-IN-5 reduces RAC1-GTP levels, suppresses AKT hyperactivation, limits sphere migration areas, and inhibits colony formation in TNBC MDA-MB-468 luciferase (Luc) cells (IC 50 = 2.1 μM). Rac1-IN-5 also exhibits anti-invasive properties in human breast CAF spheroids at 10 μM.

Rac1-IN-5 (Compound A41) administered at 25 mg/kg via intraperitoneal injection once daily for 4 weeks can prevent cancer cell metastasis in a mouse TNBC model. Additionally, Rac1-IN-5 at the same dosage and method of administration over 15 days can inhibit the metastasis of aggressive cancer in a CT26 cell xenograft BALB/c female mouse model.