Tubulin polymerization-IN-82 is a tubulin inhibitor that effectively hinders cell migration and invasion. It induces apoptosis (cellular self-destruction) through pathways mediated by mitochondrial and endoplasmic reticulum stress. Tubulin polymerization-IN-82 exhibits antitumor activity against drug-resistant cancer cells and suppresses tumor growth, making it suitable for liver cancer research.

Tubulin polymerization-IN-82 (Compound 9n) demonstrates antiproliferative activity against various cell lines at concentrations of 0.039-2.5 μM over 72 hours, with IC50 values of 0.09 μM for HepG-2, 0.25 μM for NCI-H460, 0.20 μM for HCT-116, and 0.18 μM for SK-OV-3. In resistant cells, it shows antiproliferative effects with IC50 values of 0.29 μM for A549/CDDP, 0.45 μM for A549/Paclitaxel, and 0.51 μM for MCF-7/DOX. Tubulin polymerization-IN-82 inhibits tubulin polymerization of purified tubulin at concentrations of 1.25-20 μM over 5-65 minutes, with an IC50 of 3.56 μM. It induces apoptosis in HepG-2 cells by disrupting the microtubule network through mitochondrial and endoplasmic reticulum stress pathways at 1.25 μM and 2.5 μM within 24 hours. The compound also causes G2/M phase cell cycle arrest in a concentration-dependent manner, reduces matrix metalloproteinase (MMP) levels, and induces reactive oxygen species (ROS) generation in HepG-2 cells. Additionally, it increases intracellular Ca2+ levels and upregulates the expression of p-PERK, p-eIF2α, and CHOP. Tubulin polymerization-IN-82 is hydrolyzed by esterases after 4 hours of carboxylesterase action and remains stable in PBS (pH = 7.4) and DMEM with 1% DMF over 24, 48, or 72 hours.

Compound 9n, also known as Tubulin polymerization-IN-82, administered intravenously at doses of 15 or 30 mg/kg over a period of 21 days, effectively inhibits tumor growth in the HepG-2 xenograft model.