Tubulin polymerization-IN-79 (Compound C20) acts as an inhibitor of microtubule polymerization. It exhibits significant antiproliferative activity against esophageal cancer cells, such as KYSE450 (IC50=0.36 µM) and EC-109 (IC50=0.63 µM). In esophageal cancer cells, Tubulin polymerization-IN-79 occupies the colchicine binding site, disrupting the microtubule networks integrity, activating the Hippo signaling pathway, downregulating the oncogenic protein YAP, and inducing G2/M phase arrest and apoptosis. This compound shows promise for esophageal cancer research.