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Overall screening strategy. Compound libraries are subjected to a high-throughput whole-cell transcription rescue screen to identify compounds that restore BAP1 target gene expression in cells knocked down for BAP1. Compounds that pass this screen are tested for their ability to rescue a BAP1-deficient phenotype and simultaneously screened for toxicity in a Xenopus embryo model. The lead compound is tested for its ability to halt tumor growth in a mouse model of uveal melanoma.
