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 cancerIn VitroVT103 (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 IC 50 of 1.02 nM in YAP reporter assay. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoVT103 (0.3~10 mg/kg; p.o. once per day) blocks tumor growth even at 0.3 mg/kg. Pharmacokinetics of VT103 in mice 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 (%) C max (ng/mL) C 24 hours (ng/mL) 13.2 4.5 4.7 20.0 14.9 75 896 (1 hour) 340 MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: NCI-H226-tumor bearing mice Dosage: 0.3~10 mg/kg Administration: P.o. once per day Result: Blocked tumor growth even at 0.3 mg/kg.Form:SolidIC50& Target:TEAD1 Palmitoylation