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SL-172154 + azacitidine + venetoclax is an investigational triple-drug combination studied primarily for acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (MDS). SL-172154 is a hexameric bispecific fusion protein linking the extracellular domains of SIRPα and CD40L via an inert Fc fragment. Its mechanism involves simultaneous competitive inhibition of CD47 to promote tumor cell phagocytosis and activation of CD40 to stimulate antigen processing and cross-presentation by antigen-presenting cells for enhanced antitumor immunity. Azacitidine is a hypomethylating agent (nucleoside analogue) that incorporates into DNA and RNA leading to cytotoxicity and reactivation of silenced genes. Venetoclax is a selective small-molecule inhibitor of BCL-2, restoring apoptotic processes in malignant cells. This combination is administered intravenously and orally, and is being developed for patients who are ineligible for intensive induction therapy, showing antitumor efficacy and immunomodulatory effects in early-phase clinical trials[1][2][3][4][5][7].
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