MYF-03-176 is an orally active TEAD1/3/4 inhibitor with IC₅₀ values of 47/32/71 nM, respectively. It also inhibits TEAD transcriptional activity and cell growth in NCI-H226 cells, exhibiting antitumour activity in malignant pleural mesothelioma (MPM) cells with defective Hippo signalling and in mouse xenograft models.

TEAD4:71 nM, TEAD2:275 nM, TEAD3:32 nM, TEAD1:47 nM

MYF-03-176 (0.1-10⁵ nM) acted on NCI-H226 cells for 72 hours and inhibited TEAD transcriptional activity with an IC₅₀ of 11 nM [1].
When treated with MYF-03-176 (20-500 nM) for 24 hours, it significantly downregulated the expression of YAP target genes CTGF, CYR61, and ANKRD1 while upregulating BMF expression. This result indicates its inhibitory effect on malignant mesothelioma of pleura (MPM) cells with Hippo signaling pathway defects [1].
MYF-03-176 (0-10⁴ nM) acted on NCI-H226 cells for 5 days and inhibited cell growth, with a corresponding IC₅₀ value of 9 nM [1].
When treated with MYF-03-176 (0-5 μM) for 10-14 days in combination with KRAS G12C and KRAS G12D inhibitors across multiple cell lines, it exhibited significant synergistic effects [3].

In the human mesothelioma NCI-H226 cell-derived xenograft (CDX) model, MYF-03-176 was administered orally at a dose of 30-75 mg/kg, twice daily for 28 consecutive days, and exhibited potent antitumor activity [1].
In the SW1753 xenograft BALB/c nude mouse model, when MYF-03-176 was administered orally at a dose of 100 mg/kg, twice daily for 21 consecutive days in combination with AMG510, it could effectively reduce tumor volume without affecting the body weight of nude mice [3].