ATP-Competitive inhibitors do not inhibit a kinase's non-catalytic, scaffolding roles. Instead, this goal may be accomplished by targeted protein degradation.
In this work, we report the first cell-active inhibitors/probes that target LRRK2 and AURKA noncovalently and covalently.
A ligand-centred strategy combined with phenotypic screening was used to develop novel antiproliferative inhibitors against oesophageal cancer and identified a lead compound that induces potent anticancer activity and inhibits Aurora kinase A.
Fluorescent DHP–DHPM hybrids demonstrated potent and selective antitumor activity against PC3 prostate cancer cells. Studies revealed selective inhibition of Aurora kinase C, G0/G1 cell cycle arrest and modulate MAPK, AKT, and mTOR signaling pathways.
We propose a computational framework to explore pocket-aware inhibitors targeting the J pocket of BTK kinase by integrating generative deep learning, molecular docking, and molecular dynamics simulations.