OP449

**OP449** is a specific, cell-penetrating peptide antagonist of the SET oncoprotein, which potently inhibits PP2A (protein phosphatase 2A), a tumor suppressor frequently suppressed in hematologic malignancies. By binding SET and relieving its inhibition of PP2A, OP449 restores phosphatase activity, leading to dephosphorylation and degradation of oncogenic drivers like BCR-ABL1 (including TKI-resistant mutants), STAT5, AKT, and others, thereby selectively inhibiting proliferation and inducing apoptosis in leukemia cells while sparing normal hematopoietic progenitors. It demonstrates preclinical efficacy alone or synergistically with tyrosine kinase inhibitors (TKIs) in CML (chronic myeloid leukemia), AML (acute myeloid leukemia), CLL, T-ALL, and various solid tumors including neuroblastoma, prostate, pancreatic, breast, and oral cancers, with reduced tumor burden in xenograft models.[1][2][3][4]