We next pursued identification of the protein targets of PA (1) in cells by tandem mass tags (TMT)-based proteomics . Specifically, we aimed to identify proteins that were substantially enriched (>2fold) by PA-DA over ePA-DA and competed (>5-fold) by PA (1) but not the inactive epimer ePA (Fig. and Fig. , Table -S7) in both Jurkat and HCC1806 cells. We identified only one protein, 60s ribosomal export protein NMD3 in both cell lines that fulfilled these criteria. We verified this interaction by chemoprecipitation (ChP), where the labeling of endogenous NMD3 by PA-DA (35-2) could be blocked by excess PA (1), but not excess ePA , and little to no labeling was observed in the absence of UV irradiation or with ePA (38) (Fig. and Fig. ), suggesting that PA (1) selectively and non-covalently binds to NMD3 in cells. NMD3 is an adaptor of 60S ribosomal subunit nuclear export and is released upon pre-60S maturation in the cytosol and subsequent polysome formation, though the precise mechanism of this regulation is not fully elucidated . Notably, we observed that NMD3deficient Jurkat and HeLa cells were less prone to the cytotoxic effects of PA (1), compared to control cells (Fig. , Fig. ), suggesting that NMD3 is necessary for its activity. As NMD3 is required for nascent 60S ribosome maturation (41), we next examined whether PA (1) affects ribosome assembly. Here, we observed that in Jurkat cells treated with PA (1), but not inactive ePA , led the accumulation of 80S monosomes and disomes as well as the blockade of polysome formation (Fig. , Fig. ). Further, we observed that eukaryotic translation initiation factor 6 (eIF6), an essential factor of 60S maturation and 80S assembly which is reported to be modulated by NMD3 , is localized in the 60S fraction and decreased in RNA-free fractions in cells treated with PA (1) (Fig. , Fig. ). Together, these data suggest that PA (1) engages NMD3, which results in increased 60S associated eIF6, stabilization of 80S, and subsequent impairment of polysome formation (Fig. ), likely leading to cell cycle arrest and apoptosis .