AA26-9

AA26-9 is synthesized based on a piperazine scaffold shown previously to inhibit serine hydrolases in the context of p-nitrophenoxy carbamate. AA26-9-inhibited enzymes originated from diverse functional subclasses of serine hydrolases, including lipases/phospholipases (AADACL1, ABHD6, ESD, FAAH, PAFAH2, LYPLA3), peptidases (APEH, PRCP, CTSA), thioesterases (LYPLA1, LYPLA2), and uncharacterized enzymes (ABHD11, ABHD13, BAT5). AA26-9 inhibits one of its enzyme targets LYPLA1 by covalent carbamoylation of the enzyme’s serine nucleophile (S114). AA26-9 inhibits 1/3 of the over 40 serine hydrolase found in T-cells.