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KT-253 is a highly potent and selective small molecule that degrades MDM2 protein, effectively eliminating malignant hematopoietic stem/progenitor cells (HSPCs) in myelofibrosis (MF). Unlike traditional MDM2 small-molecule inhibitors (SMIs), KT-253 overcomes the compensatory p53-dependent feedback loop that typically restores MDM2 expression, resulting in superior apoptosis induction and depletion of MF progenitor cells at significantly lower concentrations. These findings support the potential of KT-253 as a transformative therapeutic agent in MF management.
