Evaluation of EED Inhibitors as a Class of PRC2-Targeted Small Molecules for HIV Latency Reversal.

In total CD4+ T-cells isolated from 5 healthy donors, we observed no significant toxicity at 72 or 96 h after treatment with EED226 (up to 20 μM), A-395 (up to 20 μM), or GSK-343 (up to 5 μM), while we observed a minor decrease in viability at 5 μM UNC1999 ( Figure 8 A and 8 B), consistent with toxicity at this dose of UNC1999 in Jurkat cells. We observed no major change in the expression of either CD69 or CD25 in treated cells at 72 ( Figure 8 C) or 96 h ( Figure 8 D), although a slight trend toward activation in 5 μM UNC1999 treated cells was observed which is consistent with the toxicity data.

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The response to 10 μM EED226 alone in 2D10 cells was modest but reproducible, inducing a 1.8-fold increase in GFP expression over DMSO treatment as determined by flow cytometry but failed to achieve significance over the equivalent UNC5679 treatment ( Figure 1 D, n = 7).

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