Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus

We present our findings based on mining small molecule kinase inhibitors for activity against S. aureus and confirm sorafenib as one of the most potent hits. Chemical dissection of the sorafenib scaffold by organic synthesis of 72 analogs resulted in a compound (PK150) with potent anti-MRSA activity, lack of resistance development, killing of persisters, elimination of established biofilms, and in vivo efficacy in a mouse model. Within this submission the results of the whole genome sequencing assay.