SWTX-143 is an orally active YAP/TAZ-TEAD inhibitor that binds to the palmitoylation pocket of all four TEAD isoforms. SWTX-143 causes irreversible and specific inhibition of the transcriptional activity of YAP/TAZ-TEAD and shows antitumor activity.
SWTX-143 (5-207 nM, 6 days) inhibits the proliferation of NF2-deficient mesothelioma cells, with IC50 values ranging from 5 to 207 nM[1]. SWTX-143 (12 nM, 24 hours) selectively inhibits TEAD transcription factor activity in HEK293 cells, with an IC50 of 12 nM[1].
SWTX-143 (10, 25, 50 mg/kg, p.o., once daily for 19 days) induces dose-dependent tumor reduction in the NCI-H226 xenograft nude mouse model without notable side effects[1].
References:
[1]. Hanne Hillen, et al. A novel irreversible TEAD inhibitor, SWTX-143, blocks Hippo pathway transcriptional output and causes tumor regression in preclinical mesothelioma models. Mol Cancer Ther. 2023 Sep 23.