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Image depicting molecular docking of venetoclax (pink structure) and conjugate A1 (blue structure) bound to Bcl-2 (Protein Data Bank [PDB] code: 6O0K) and Bcl-xL (PDB code: 4QNQ). Venetoclax and A1 made a critical similar hydrogen bond between the azaindole moiety and Bcl-2 D103, and the introduced dihydroartemisinin fragment of A1 formed a novel hydrogen bond with Bcl-2 R106 (upper Figure). A1 and venetoclax bound to Bcl-xL with a similar binding mode at the P2 pocket Bcl-xL, but a markedly different mode at the P4 pocket, which led to a significant reduction in potency against Bcl-xL (lower Figure). See the article by Zhang et al.