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Bifunctional degraders of BRPF1 that retain the antiproliferative Phenotype

The BRPF (Bromodomain and PHD Finger-containing) family of proteins consisting of BRPF1 and BRPF2/BRD1, are important epigenetic proteins in the assembly of the MYST-family histone acetyltransferase complexes, specifically MOZ and MORF1. These chromatin-modifying complexes can lead to altered expression of genes that drive innate immunity, inflammation, cancer, and neurological disorders. Histone Acetyltransferase (HAT) complexes are associated with chromosomal translocations known to contribute to the development of Acute Myeloid Leukemia (AML) and the leukemia-derived fusion proteins such as MOZ-TIF2are known to promotoe self-renewal of leukemic stem cells.

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