Ferroptosisinducer-9 is an agent that induces ferroptosis and acts as a microtubule polymerization inhibitor at the colchicine binding site. It inhibits MCF-7 cell growth with an IC50 of 14 nM and reduces [3H]colchicine binding. The compound decreases GPX4 and FTH expression while increasing COX2 and ACSL4 levels; it also lowers GSH, NADP+, and NADPH, and raises LPO, MDA, and Fe(II) concentrations, alongside reducing SOD levels. Ferroptosisinducer-9 demonstrates significant antitumor efficacy in HCT116 CRC xenograft models and is applicable in the study of triple-negative breast cancer (TNBC) and colorectal cancer (CRC).

Ferroptosis inducer-9 (Compound 12) inhibits tubulin polymerization with an IC 50 of 550 nM and suppresses the growth of MCF-7 cells with an IC 50 of 14 nM. At concentrations of 0.3-1 μM, it causes complete growth arrest and notable changes in nuclear and cytoskeletal morphology in H2BC11-moxGFP/sTagRFP-TUBA1B labeled MDA-MB-231 cells. Ferroptosis inducer-9 inhibits growth in SW620, SW480, HCT116, HepG2, and CC-2509f cells with respective IC 50 values of 0.633 μM, 0.0654 μM, 0.389 μM, 107.3 μM, and 52.9 μM. It downregulates the expression of ferroptosis inhibitors (SLC7A11, SLC3A2, SLC11A2, NRF2, NCOA4, KEAP1, GPX4, FTL, FTH1) and upregulates ferroptosis promoters (PTGS2, NOX1, COX2, COX4, ACSL4) in HCT116 cells. Furthermore, Ferroptosis inducer-9 decreases concentrations of GSH and SOD, lowers NADP+ and NADPH levels, and increases LPO, MDA, Fe(II), and GSSG concentrations.

A significant antitumor effect is observed in nude mice bearing HCT116 colorectal cancer xenografts when administered ferroptosis inducer-9 (Compound 12) (25 mg/kg, intraperitoneal injection, once every 2 days for 30 days).