Figure 4. . Snow White effect.

(A) Venetoclax mimics BH3-only proteins, the native ligands of BCL-2 and apoptosis activators, by binding to the hydrophobic groove of BCL-2 proteins, thereby repressing BCL-2 activity and restoring apoptotic processes in tumor cells. Venetoclax is an effective treatment option, even in high-risk patients with chronic lymphocytic leukemia. BH3-only proapoptotic proteins favor the activation of the BAX protein, which creates pores in the mitochondria so that the cytochrome C protein is secreted, and apoptosis is triggered. BCL-2 protein inhibits both proapoptotic proteins BH3-only and BAX, preventing apoptosis. Venetoclax (poisoned apple) simulates an increase in proaptotic proteins causing BCL-2 to bind to venetoclax, leaving free proaptotic proteins that induce membrane permeability and cytochrome C output. (B) ‘The Snow White effect’. The drawing represents the poisoned apple of venetoclax, which binds to BCL inhibiting its protective function, promoting the apoptosis of tumor cells.

BCL-2: B cell lymphoma 2.