We also characterize a novel, non-COX inhibitory sulindac derivative, referred to as ADT-094 that potently and selectivity inhibits colon tumor cell growth by inhibiting PDE5 and 10 and activating cGMP/PKG signaling to suppress β-catenin/TCF-transcriptional activity, resulting in cell cycle arrest and apoptosis induction. Here, PRKG1 is linked to colonic neoplasm.