Tubulin polymerization-IN-84 inhibits tubulin polymerization by targeting the colchicine-binding pocket, with an IC50 = 10.9 μM. Tubulin polymerization-IN-84 shows antiproliferative activity against Jurkat, B16-F10, HCT116, and MDA-MB-231 cells ( IC50 = 60 nM, 380 nM, 138 nM, and 1.054 μM). Tubulin polymerization-IN-84 induces G2/M-phase arrest and apoptosis in B16-F10 cells. Tubulin polymerization-IN-84 suppresses tumor growth in a B16-F10 melanoma model and potentiates anti-tumor immunity in combination with a PD-L1 mAb for the research of T-cell acute lymphoblastic leukemia, melanoma, colon cancer, and breast cancer.
In Vivo, Tubulin polymerization-IN-84 (compound 5b) (10 mg/kg; i.p.; QD; 14 days) inhibits tumor growth in C57BL/6 mice bearing established B16-F10 melanoma tumors (TGI = 27.5%), and shows enhanced efficacy in combination with a PD-L1 mAb (10 + 10 mg/kg; TGI = 36.2%) without significant body-weight loss[1].
In Vitro, Tubulin polymerization-IN-84 (compound 5b) (48 h) inhibits proliferation of Jurkat, B16-F10, HCT116, and MDA-MB-231 cells (IC50 = 60 nM, 380 nM, 138 nM, and 1.054 μM)[1]. Tubulin polymerization-IN-84 (0.1-5 μM; 24 h) dose-dependently suppresses wound closure/migration and colony formation of B16-F10 cells[1]. Tubulin polymerization-IN-84 (0.5-5 μM; 48 h) induces both G2/M-phase arrest and apoptosis in B16-F10 cells (G2/M: 9.75% in control vs 81.1% at 5 μM)[1]. Tubulin polymerization-IN-84 directly binds to β-tubulin (KD = 31.84 μM)[1]. Tubulin polymerization-IN-84 (0.1-5 μM) competes with EBI for binding to the colchicine-binding site of β-tubulin in B16-F10 cells in a concentration-dependent manner[1]. Tubulin polymerization-IN-84 (0.5-5 μM; 12 h) induces disassembly of cytoplasmic microtubule networks in B16-F10 cells[1]. Tubulin polymerization-IN-84 (0.5-5 μM; 6 h) dose-dependently disrupts HUVEC capillary-like network formation on Matrigel and reduces junctions/nodes[1].
References:
[1]. Cheng B, et al. Novel imidazo[1,2-a]pyridine-based tubulin polymerization inhibitors: Structure-activity relationships and anti-tumor immune potentiation. Eur J Med Chem. 2026;302(Pt 2):118356. doi:10.1016/j.ejmech.2025.118356
In Vivo, Tubulin polymerization-IN-84 (compound 5b) (10 mg/kg; i.p.; QD; 14 days) inhibits tumor growth in C57BL/6 mice bearing established B16-F10 melanoma tumors (TGI = 27.5%), and shows enhanced efficacy in combination with a PD-L1 mAb (10 + 10 mg/kg; TGI = 36.2%) without significant body-weight loss[1].
In Vitro, Tubulin polymerization-IN-84 (compound 5b) (48 h) inhibits proliferation of Jurkat, B16-F10, HCT116, and MDA-MB-231 cells (IC50 = 60 nM, 380 nM, 138 nM, and 1.054 μM)[1]. Tubulin polymerization-IN-84 (0.1-5 μM; 24 h) dose-dependently suppresses wound closure/migration and colony formation of B16-F10 cells[1]. Tubulin polymerization-IN-84 (0.5-5 μM; 48 h) induces both G2/M-phase arrest and apoptosis in B16-F10 cells (G2/M: 9.75% in control vs 81.1% at 5 μM)[1]. Tubulin polymerization-IN-84 directly binds to β-tubulin (KD = 31.84 μM)[1]. Tubulin polymerization-IN-84 (0.1-5 μM) competes with EBI for binding to the colchicine-binding site of β-tubulin in B16-F10 cells in a concentration-dependent manner[1]. Tubulin polymerization-IN-84 (0.5-5 μM; 12 h) induces disassembly of cytoplasmic microtubule networks in B16-F10 cells[1]. Tubulin polymerization-IN-84 (0.5-5 μM; 6 h) dose-dependently disrupts HUVEC capillary-like network formation on Matrigel and reduces junctions/nodes[1].
References:
[1]. Cheng B, et al. Novel imidazo[1,2-a]pyridine-based tubulin polymerization inhibitors: Structure-activity relationships and anti-tumor immune potentiation. Eur J Med Chem. 2026;302(Pt 2):118356. doi:10.1016/j.ejmech.2025.118356