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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.

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.
VT103 results in the disappearance of palmitoylated TEAD1 with a concomitant increase in unpalmitoylated TEAD1.
VT103 shows an IC₅₀ of 1.02 nM in YAP reporter assay.

VT103 (0.3~10 mg/kg; p.o. once per day) blocks tumor growth even at 0.3 mg/kg.
Pharmacokinetics of VT103 in mice

Room temperature in continental US; may vary elsewhere.

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