<i>In vitro</i> activity (<i>Wolbachia</i> EC₅₀) and drug exposure levels (rat pharmacokinetic studies) for Tylosin analogs.

Representative TylA analogs were evaluated for anti-Wolbachia activity using a high-content imaging system in insect cells; replicate experiments were averaged to determine an EC50 value for each compound (column 2). A subset of analogs were dosed PO to Sprague-Dawley rats, with plasma drug levels recorded at regular intervals to determine total AUC of parent drug (column 3) and of the primary metabolite TylA (column 4). Potency-weighted AUC (column 5) and time-over-EC50 (column 7; measured as EC50-multiple at 8 hrs) are taken as predictors of in vivo activity, and were used to prioritize compounds for further study.