A paradigm shiftingPPI modulator was demonstrated by scientistsat Abbvie to target antiapopototic protein B-cell lymphoma 2 (BCL2).BCL2 binds the BH3 domain of pro-apoptotic Bax via an α-helicalsequence (Figure A).A BH3 mimetic, Venetoclax, was discovered by a fragment-based drugdiscovery (FBDD) campaign and functions by inhibiting BCL-2 mediatedPPIs, which restores the apoptotic pathway in cancer cells and leadsto death. This evidence concerns the gene BCL2 and cancer.