Jeffrey M. McKenna

An Optimized RNF126-Targeting Covalent Handle for Molecular Glue Degraders

This paper develops an optimized covalent handle targeting RNF126 to create molecular glue degraders, showing improved selectivity and reduced cytotoxicity compared to a fumarate-based handle.

Stereoselective Covalent Targeting of BTK(C481S) and Kinases with β-Lactone Electrophiles

This paper develops stereoselective β-lactone electrophiles to covalently target BTK(C481S) and other kinases, showing enantiomers engage distinct kinome subsets.

Targeted Transcriptional Repression by Induced Proximity

This paper introduces TRACERs, small-molecule drugs that silence transcription factors in cancer by recruiting repressor complexes, showing efficacy against ER and AR in breast and prostate cancer.

Sulfinyl Aziridines as Stereoselective Covalent Destabilizing Degraders of the Oncogenic Transcription Factor MYC

This paper identifies a sulfinyl aziridine compound that selectively degrades MYC by targeting specific residues in its intrinsically disordered regions, demonstrating the potential of chiral small molecules for targeting undruggable proteins.