WIKI4 is a potent tankyrase inhibitor with an IC50 of 26 nM for TNKS2. WIKI4 potently inhibits Wnt/β-catenin signaling and that its half-maximal response dose is 75 nM. WIKI4 mediates its effects on Wnt/β-catenin signaling by inhibiting the enzymatic activity of TNKS2[1][2]. WIKI4 is cytotoxic to SCLC cells with an IC50 value of 0.02 μM[3].
WIKI4 (100 nM, 1 μM; 6 days; DLD1 cells) inhibits growth of DLD1 cells relative to DMSO controls in media containing low serum. WIKI4 inhibits expression of β-catenin target genes and cellular responses to Wnt/β-catenin signaling[1].WIKI4 (1 μM; 2 hours, 4 hours, 6 hours, or 24 hours; DLD1 cells) significantly increases the steady-state abundance of AXIN1 and AXIN2[1].
References:
[1]. James RG, et al. WIKI4, a novel inhibitor of tankyrase and Wnt/ß-catenin signaling. PLoS One. 2012;7(12):e50457.
[2]. Haikarainen T, et al. Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4. PLoS One. 2013 Jun 6;8(6):e65404.
[3]. Sadava D, et al. The effect of brassinolide, a plant steroid hormone, on drug resistant small-cell lung carcinoma cells. Biochem Biophys Res Commun. 2017 Nov 4;493(1):783-787.