Peptide-54

Peptide-54 is a rationally designed competitive peptide engineered to disrupt the interaction between the transcription factors MEF2C and MEF2D. This interaction is critical for the stability and maintenance of leukemic cells in KMT2A-rearranged Acute Myeloid Leukemia (AML). By interfering with MEF2C-MEF2D binding, Peptide-54 leads to the co-degradation of both MEF2C and MEF2D, induction of myeloid differentiation, and suppression of leukemic proliferation. Its therapeutic effects are mediated through the CUL2-ZYG11B/ZER1 degradation axis, which targets MEF2C for proteolysis. Preclinical studies in a murine MLL-AF9 AML model demonstrated that Peptide-54 significantly delayed disease progression, reduced leukemia burden, and extended overall survival, while selectively sparing normal hematopoietic progenitor cells.