SSE15206 is a microtubule polymerization inhibitor that overcomes multidrug resistance, causing aberrant mitosis and resulting in G2/M arrest due to incomplete spindle formation in cancer cells.

Microtubule:197 nM (GI50)

Treatment of cells with SSE15206 causes aberrant mitosis resulting in G2/M arrest due to incomplete spindle formation, a phenotype often associated with drugs that interfere with microtubule dynamics. SSE15206 is able to overcome resistance to chemotherapeutic drugs in different cancer cell lines including multidrug-resistant KB-V1 and A2780-Pac-Res cell lines overexpressing MDR-1, making it a promising hit for the lead optimization studies to target multidrug resistance.

Fluorescence intensity of tubulin (4?μM) in the presence of colchicine (20?μM) and SSE15206 at indicated concentrations was measured. DMSO was used as a solvent control while 50?μM nocodazole was used as a positive control for colchicine displacement. Samples were incubated for 60?min at 37℃before measurement of fluorescence (excitation at 355?nm and emission at 460?nm). KB-V1 and A2780-Pac-Res cells were incubated with 5?μM rhodamine, for 1?hour at 37℃in the presence or absence of inhibitors. Cells were then washed twice with PBS and incubated in the efflux medium (their respective growth media) in the presence of DMSO, 20?μM verapamil, and 10?μM SSE15206 for 3?hours. The percentage of rhodamine 123 positive cells was determined . Experiments were done in duplicates with 4–5 readings for each sample in each experiment.