We have presented P2As as a first-in-class agents that suppress penicillinase expression. This is an innovative approach towards developing penicillin G enhancers. Our very early hits are extremely potent, and already virtually eliminate penicillinase, even though they are not quite as potent as recent discoveries such as loratadine that have the same ability. At the same time, loratadine functions via Stk1 -a well-validated target. P2As function differently. VraS, another validated target for β-lactam enhancement, is also not the target. Our very early structure-function study suggests the target is a single entity, although we cannot discount the possibility that similar binding pockets across more than one target could also exist. On the other hand, it seems P2As act at a global regulator either upstream or downstream of multiple signal transduction pathways, as multiple kinase knockouts abrogated their activity -this, and the parallel retention of activity against Δstk1, ΔvraS and ΔsrrB strains, suggests this is not non-specific toxicity.