ETS-005

ETS-005 is a highly selective small molecule inhibitor of TEAD4 palmitoylation, developed by ETERN Therapeutics. It targets the Hippo signaling pathway by binding to the palmitoylation pocket of TEAD4 with over 15-fold selectivity compared to other TEAD paralogs. By inhibiting TEAD4, ETS-005 disrupts the YAP/TAZ-TEAD transcriptional complex, which is often aberrantly activated in various solid tumors, including those with NF2 or LATS1/2 mutations. The compound demonstrates potent anti-tumor activity, favorable oral bioavailability, and significant brain penetration. It is currently in IND-enabling studies for the treatment of solid tumors and mesothelioma, with potential for combination therapy with MAPK and RTK inhibitors.