S227928 + venetoclax

S227928 + venetoclax is an investigational **combination therapy** being developed for the treatment of **acute myeloid leukemia (AML)**, **myelodysplastic syndromes (MDS)/AML**, and **chronic myelomonocytic leukemia (CMML)**. **S227928** is a novel anti-CD74 antibody-drug conjugate (ADC) that targets CD74 on malignant cells and delivers an MCL-1 inhibitor as its cytotoxic payload. The ADC selectively binds to CD74-expressing cells, leading to internalization and intracellular release of the MCL-1 inhibitor payload (S64315), which disrupts the MCL-1/BIM complex, promotes mitochondrial apoptosis, and induces cell death in AML models. **Venetoclax** is a selective BCL-2 inhibitor approved for AML and is known for promoting apoptosis in cancer cells. The combination of S227928 and venetoclax has demonstrated potent, synergistic anti-leukemic activity in preclinical AML models, including those with TP53 mutations and subgroups with intrinsic resistance to venetoclax. This therapy is under investigation in clinical trials, with demonstrated activity dependent on CD74 expression levels[1][2][3][4].

Other names

S227928 in combination with venetoclaxS-227928 in combination with venetoclaxS 227928 in combination with venetoclax