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, 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].
VT103 (0.3~10 mg/kg; p.o. once per day) blocks tumor growth even at 0.3 mg/kg[1].
Pharmacokinetics of VT103 in mice[1]
| Dose | IV | PO |
| 7 mg/kg | T1/2 (hours) | Vdss (L/kg) | CI(mL/min/kg) | AUC 0-24 hours (μg*h/mL) | AUC 0-24 hours (μg*h/mL) | Oral availability (%) | Cmax (ng/mL) | C24 hours (ng/mL) |
| 13.2 | 4.5 | 4.7 | 20.0 | 14.9 | 75 | 896 (1 hour) | 340 |
| Animal Model: | NCI-H226-tumor bearing mice[1] |
| Dosage: | 0.3~10 mg/kg |
| Administration: | P.o. once per day |
| Result: | Blocked tumor growth even at 0.3 mg/kg.
|
[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.
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