FIG 1.

Latency reversal activity of straight-chain saturated and unsaturated ingenol-C-3-esters. Linear esters were added to the 3-carbon position of the ingenol core molecule (full and abbreviated nomenclature shown in panel A, along with ingenol core structure in black and esters in color), with the exception of ingenol-3-hexanoate, which was obtained from the UNC Care Collaboratory Pharmacology Core. Straight-chain ingenol-3-esters were tested for latency reversal efficacy using a latent HIV-1 cell line (J-Lat 10.6) containing a full-length integrated HIV-1 provirus that expresses green fluorescent protein (GFP) upon proviral transcription. Jurkat cells were exposed to compounds across a dose range from 1 nM to 3,000 nM. After 24-hour exposure, flow cytometry was performed to quantify GFP-positive cells, which was compared to positive control (PMA stimulation) to obtain percent maximal HIV-1 reactivation. (B) Fitted dose-response curves with median and 95% confidence intervals are based on five independent in vitro experiments.