W478

W478 is a novel small molecule inhibitor of Serine hydroxymethyltransferase 2 (SHMT2), identified for its potential in treating esophageal carcinoma. It demonstrates potent SHMT2 inhibition with an IC50 value of 1.21 μM and binds tightly to SHMT2 (KD = 10.6 ± 1.2 μM) at the folate binding site. In human esophageal cancer cell lines (KYSE-450 and KYSE-70), W478 exhibits significant antiproliferative effects (IC50 = 1.62 μM and 1.18 μM, respectively), inhibits migratory and invasive potential, induces G2/M phase cell arrest, and promotes cell apoptosis and reactive oxygen species production. These findings suggest W478 as a promising lead compound for SHMT2-targeted esophageal cancer therapy.