In NCI-H1703 and A549 cells, SYL2158 (66) induced NSD3 degradation and effectively inhibited H3K36 methylation, the expression of NSD3-associated genes, and clone formation in lung cancer cells, in addition to possessing good selectivity over the other two NSD proteins (NSD1 and NSD2). This evidence concerns the gene NSD3 and lung carcinoma.