Abstract: Sulfonyl-triazole compounds and related sulfonyl-heterocycle compounds are described. The compounds can form covalent adducts with reactive nucleophilic amino acid residues, e.g., reactive tyrosines and reactive lysines, in kinases to form modified kinases and/or alter the biological activity of the kinases. Kinases targetable by the compounds include cyclin-dependent kinase 2 (CDK2), diacylglycerol kinases (DGKs), and phosphofructokinase (PFK). Pharmaceutical compositions including the compounds and methods of inhibiting kinases are also described.

Abstract: Purine-derived covalent probes (e.g., halo or di-halo-substituted purine based covalent probes) and related ligands are described. The compounds can be used to identify reactive nucleophilic amino acid residues, such as reactive cysteine residues, in proteins and to modify the activity of proteins with reactive nucleophilic amino acid residues (e.g., reactive cysteine residues) via the formation of protein adducts comprising the ligands Modified proteins prepared from the probes and ligands are also described.