LF3 is an inhibitor of the protein-protein interaction between β-catenin and T cell factor 4 (TCF4).1 It inhibits the β-catenin-TCF4 interaction in an immunoprecipitation assay and prevents β-catenin-induced inhibition of SCN5A promoter activity in HEK293 cells when used at a concentration of 10 ?M. LF3 increases levels of the voltage-gated sodium channel Nav1.5 in HL-1 cardiomyocytes. It is cytotoxic to GES-1, HGC-27, MKN45, and AGS gastric cancer cells (IC50s = 24.68, 18.2, 489, and 56.76 ?M, respectively).2 In vivo, LF3 (25 mg/kg) decreases pulmonary artery systolic pressure (PASP) and the right ventricular hypertrophy index (RVHI) in a rat model of total pneumonectomy-induced pulmonary hypertension.3
1.Zhao, L., Sun, L., Lu, Y., et al.A small-molecule LF3 abrogates β-catenin/TCF4-mediated suppression of NaV 1.5 expression in HL-1 cardiomyocytesJ. Mol. Cell. Cardiol.13590-96(2019) 2.Yu, Z., Jiang, X., Qin, L., et al.A novel UBE2T inhibitor suppresses Wnt/β-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitinationOncogene40(5)1027-1042(2021) 3.Lei, Y., Yang, Q., Nie, Y., et al.Small-molecule inhibitor LF3 restrains the development of pulmonary hypertension through the Wnt/β-catenin pathwayActa Biochim Biophys. Sin. (Shanghai)53(10)(2021)