ZINC69391, a specific Rac1 inhibitor, interferes with Rac1-GEF interaction by masking Trp56 residue on Rac1 surface. ZINC69391 interferes with the interaction of Rac1 with Dock180 and reduces Rac1-GTP levels. ZINC69391 induces apoptosis, and shows antiproliferative and antimetastatic effects[1][2][3].
ZINC69391 inhibits growth of U937, HL-60, KG1A and Jurkat cells with IC50s ranging from 41 to 54 μM[1].
ZINC69391 (50-100 μM; 24 hours) augments the enzymatic activity of caspase 3 in a concentration dependent manner[1].
ZINC69391 (0-125 μM; 72h) reduces cell proliferation of human glioma cells[2].
ZINC69391 (50-100 μM; 48 hours) triggers cell cycle arrest[2].
ZINC69391 (50 μM; 24 hours) triggers apoptosis on human acute leukemic cells[1].
Cell Proliferation Assay[2]
| Cell Line: | U-87 MG, LN229 cells |
| Concentration: | 0-125μM |
| Incubation Time: | 72 hours |
| Result: | Reduced cell proliferation in a concentration-dependent manner. |
Cell Cycle Analysis[2]
| Cell Line: | LN229 cells |
| Concentration: | 50, 100 μM |
| Incubation Time: | 48 hours |
| Result: | Resulted in a significant increased percentage of cells in the sub-G0/G1 phase in a concentration dependent manner. |
Apoptosis Analysis[1]
| Cell Line: | HL-60, U937 and KG1A cell lines |
| Concentration: | 50 μM |
| Incubation Time: | 24 hours |
| Result: | Led to a significant increase in apoptotic cells. |
ZINC69391 (25 mg/kg; i.p; daily for 21 days) impairs metastatic lung colonization in a syngeneic animal model[3].
| Animal Model: | Specific pathogen-free female BALB/c inbred mice (bearing F3II cells)[3] |
| Dosage: | 25 mg/kg body weight |
| Administration: | I.p; daily for 21 days |
| Result: | Significantly reduced by about 60% the formation of total metastatic lung colonies. |