SPA-10091-HCl is a DOT1L degrader that selectively degrades the DOT1L protein via the nuclear ubiquitin-proteasome pathway, thereby inhibiting H3K79 methylation in CRPC cells. It also inhibits DOT1L enzymatic activity (IC50 = 0.87 µM), induces apoptosis, and significantly suppresses tumor growth in vivo.
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