SU3327 was originally identified as an inhibitor of the serine/threonine c-Jun N-terminal kinases (JNKs) [1
]. It is substrate competitive (inhibiting the protein-protein interaction between JNK and the substrate JIP-1), and selective for JNK vs
. p38 MAPK and Akt. SU3327 was shown to restore insulin sensitivity in mouse models of diabetes.
In the search for new antibiotics, artificial intelligence algorithms were used to identify novel chemotypes that were likely to have novel mechanisms of antibacterial activity. SU3327 (re-named as halicin) was identified by this process and in vitro
and in vivo
follow-up showed that it potently killed a wide range of diffucult to treat, antibiotic-resistant bacterial strains [2
]. Halicin appears to disrupt the ability of bacteria to maintain an electrochemical gradient across their cell membranes which blocks their production of ATP for energy.