Multitarget inhibitors/probes that target LRRK2 and AURORA A kinases noncovalently and covalently

Herein, we report a salicylaldehyde-based, reversible covalent inhibitor (A2) that possesses moderate cellular activity against AURKA with a prolonged residence time and shows significant non-covalent inhibition towards LRRK2. Our results indicated that this multitarget kinase inhibitor may be used as the starting point for future development of more potent, selective and dual-targeting covalent kinase inhibitors against AURKA and LRRK2 for mitophagy.

Automated summary

Here, a salicylaldehyde-based reversible covalent inhibitor (A2) with moderate cellular activity against AURKA and prolonged residence time is reported. The inhibitor also shows significant non-covalent inhibition towards LRRK2. This multitarget kinase inhibitor may serve as a starting point for developing more potent, selective, and dual-targeting covalent kinase inhibitors against AURKA and LRRK2 for mitophagy.