Figure 1 | Cell Death Discovery

Figure 1

From: Close encounter of the covalent kind: Inhibiting MCL1’s proapoptotic activity with covalent inhibitors

Figure 1

Upon binding into the BH3-binding groove, compound 11 reacts with LYS234 to form a covalent bond. The design of compound 11 was based on previously reported MCL1 inhibitors, which engage MCL1 by forming a deep pocket into MCL1 and creating a charged interaction with ARG263. The covalent bond in compound 11 increases the stability of the complex between the inhibitor and the protein (IC50=4.2 nM) and, as a consequence, induces the activation of caspases 3/7 activation in MCL1 dependent MOLP-8 cells (IC50=75 nM). On the left, MCL1 is shown as surface representation (PDB entry: 3WIX).

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