Tubulin/LSD1-IN-1 is a potent dual inhibitor of tubulin polymerization and LSD1 (IC50 = 1.72 μM), exhibiting broad-spectrum antiproliferative activity against cancer cell lines. By targeting the colchicine binding site, it disrupts the microtubule network in gastric cancer cells. Tubulin/LSD1-IN-1 enhances methylation levels of H3K4me1/2 and H3K9me2/3, facilitating epigenetic regulation. It induces G2/M phase arrest, promotes apoptosis, and effectively inhibits colony formation in gastric cancer cells.

Tubulin/LSD1-IN-1 (Compound L-6) exhibits dose and time-dependent inhibition effects on MGC-803 and HGC-27 cells at concentrations ranging from 10-60 nM over 12-48 hours, reducing long-term proliferation of gastric cancer cells, while showing lower toxicity to GES-1 cells. The compound demonstrates IC50 values under 100 nM across various cancer cell lines, including MGC-803 (33 nM), HGC-27 (49 nM), HTC-116 (38 nM), and KYSE-450 (48 nM) when used for 48 hours. Tubulin/LSD1-IN-1, administered at 10-60 nM for 24-48 hours, disrupts cell cycle regulation by inhibiting tubulin polymerization and arrests cells at the G2/M phase in MGC-803 and HGC-27 cells. Additionally, the compound induces significant morphological changes and apoptosis in MGC-803 and HGC-27 cells at 20-60 nM for 48 hours. It effectively represses demethylation of H3K4me1/2 and H3K9me2/3 in these cells at 10-60 nM over 48 hours.