Beyond Acrylamide: A Structure-Guided Investigation of Covalent Warheads in the Development of CDK7 Inhibitors

Key Points

• This research aims to develop more effective and selective covalent inhibitors for CDK7.
• Designed and synthesized a series of covalent inhibitors based on the THZ1 scaffold.
• Assessed the antiproliferative activity of the inhibitors in cancer cell lines.
• Evaluated the selectivity of the inhibitors against CDK7 and other kinases.
• Identified covalent CDK7 inhibitors with significantly enhanced activity compared to existing compounds.
• Demonstrated improved selectivity profiles for the new inhibitors in preclinical tests.