sulindac sulfide amide

Sulindac sulfide amide (SSA, also known as SRI 21009) is a novel amide derivative of the nonsteroidal anti-inflammatory drug (NSAID) sulindac sulfide. It was rationally designed to eliminate cyclooxygenase (COX-1 and COX-2) inhibitory activity, thereby avoiding the gastrointestinal, renal, and cardiovascular toxicities associated with traditional NSAIDs, while enhancing anticancer potency. SSA acts through a COX-independent mechanism, primarily by inhibiting cGMP-specific phosphodiesterase 5 (PDE5) and phosphodiesterase 10 (PDE10). This leads to the accumulation of intracellular cGMP and the activation of cGMP-dependent protein kinase (PKG), which subsequently suppresses oncogenic Wnt/β-catenin and Akt/mTOR signaling pathways. Preclinical studies have demonstrated its efficacy in inducing apoptosis and autophagy in breast, colorectal, lung, and prostate cancer models.

Other names

SSAsulindac sulfide amide