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Lysosomes perform
a critical cellular function as a site of degradation
for diverse cargoes including proteins, organelles, and pathogens
delivered through distinct pathways, and defects in lysosomal function
have been implicated in a number of diseases. Recent studies have
elucidated roles for the lysosome in the regulation of protein synthesis,
metabolism, membrane integrity, and other processes involved in homeostasis.
Complex small-molecule natural products have greatly contributed to
the investigation of lysosomal function in cellular physiology. Here
we report the discovery of a novel, small-molecule modulator of lysosomal
acidification derived from diversity-oriented synthesis through high-content
screening
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