LM98

LM98 is a small-molecule inhibitor of the TEA domain (TEAD) transcription factors, developed as a potent analogue of flufenamic acid. It specifically targets the Hippo signaling pathway by binding to the highly conserved palmitate-binding pocket (PBP) of TEAD. This binding inhibits TEAD autopalmitoylation, a critical post-translational modification required for the stability of TEAD and its functional interaction with the transcriptional co-activator YAP (Yes-associated protein). By disrupting the YAP-TEAD transcriptional complex, LM98 suppresses the expression of oncogenic target genes such as CTGF and Cyr61. Preclinical evaluations in MDA-MB-231 breast cancer cells have demonstrated that LM98 effectively inhibits cell migration and induces cell cycle arrest in the S phase, highlighting its potential as a therapeutic lead for cancers driven by Hippo pathway dysregulation.