Building on publicly available data derived from a CO-ADD screen, we have investigated the promising activity against MRSA of a set of diarylimidazoles. Through synthetic variation of the core structure, we have identified simple molecules with good potency, solubility and low metabolic clearance; the identification of a metabolite was made possible by a private sector contribution to this open research project. Potency tended to correlate with toxicity to mammalian cells, and through experimental investigation of the series' mechanism of action we have identified TGF-β1 as the potential mammalian target. Two key unanswered questions that could be pursued next for this series include: 1) confirmation of the mechanism of action (both in MRSA, and in mammalian cell lines to explain toxicity) using pull-down experiments with modified versions of the compounds, a strategy requiring the addition of a tether to the structure which, based on the SAR obtained to date, could be installed in place of the methoxy group in 980, and 2) further analog synthesis rounds based on the most attractive current compound, 975. Continuation of this research along these lines is made straightforward for the community by the availability of all data and discussions, and a platform for collaboration, on the Open Source Antibiotics infrastructure.