| Description |
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].
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| Related Catalog |
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| Target |
TEAD1 Palmitoylation[1]
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| In Vitro |
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 shows an IC50 of 1.02 nM in YAP reporter assay[1].
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| In Vivo |
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.
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| 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.
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