Fig. 5
From: The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy
Clinically developed BH3-mimetics. a Overview of current clinically tested BH3-mimetics targeting BCL2, BCL-XL, MCL1 or multiple anti-apoptotic BCL2 proteins (created in Biorender). b Hydrophobic pockets P1, P2, P3 and P4 mapped onto the surface of the BCL2 structure (PDB-id: 1G5M31). c Zoom into SS55746, navitoclax, venetoclax or sonrotoclax bound to BCL2 (PDB-id: 6GL8,336 PDB-id: 4LVT,32 PDB-id: 6O0K,320 PDB-id: 8HOG). d Overlay of venetoclax bound to BCL2 (light grey) and BCL2-G101V (yellow). Mutation of glycine 101 (light grey spheres) to valine (yellow spheres) effects conformational change (indicated by black arrow) of the adjacent E152 (side chains as sticks in light grey and yellow, respectively), pushing it towards the chlorine (green) of venetoclax and slightly displacing it. (PDBids: 6O0K and 6O0L320). e 2D sketches of inhibitors shown in B-E, and pelcitoclax and lisaftoclax
