Benzenesulfonamide, N-methyl-3-(1-methyl-1H-imidazol-4-yl)-4-[[4-(trifluoromethyl)phenyl]amino]-

Biological Activity

VT103, an analog of VT101, is an orally active and selective TEAD1 protein palmitoylation inhibitor. VT103 inhibits YAP/TAZ-TEAD promoted gene transcription, blocks TEAD auto-palmitoylation, and disrupts interaction between YAP/TAZ and TEAD. VT103 can be used for the research of cancer[1]. VT103 (HEK293T cells; 3 μM) appeares to be TEAD1-selective, as it does not block palmitoylation of TEAD2, TEAD3, or TEAD4. VT103 (NF2-deficient NCI-H226 cells; 3 mmol/L; 4 or 24 hours) selectively disrupts YAP-TEAD1 interaction[1].VT103 results in the disappearance of palmitoylated TEAD1 with a concomitant increase in unpalmitoylated TEAD1[1]. VT103 (0.3~10 mg/kg; p.o. once per day) blocks tumor growth even at 0.3 mg/kg[1].

References

[1]. Tang TT, et al. Small Molecule Inhibitors of TEAD Auto-palmitoylation Selectively Inhibit Proliferation and Tumor Growth of NF2-deficient Mesothelioma. Mol Cancer Ther. 2021;20(6):986-998.