Amx-883, a potent and selective degrader of BRD9 drives differentiation in acute myeloid leukaemia and shows synergistic efficacy in combination with venetoclax In Vivo and prevents the emergence of resistance to venetoclax in vitro.
In vivo study shows amx-883 drives differentiation and reduces disease burden in acute myeloid leukaemia, suggesting potential against resistance to venetoclax.
Key Points
To evaluate the efficacy of amx-883, a brd9 degrader, in inducing differentiation and preventing resistance in acute myeloid leukaemia.
Assess in vitro effects of amx-883 on AML cell lines and normal cells
Investigate combination therapies involving amx-883 and venetoclax in AML models
Conduct in vivo studies of amx-883 in murine models of disseminated AML
Measure changes in cell surface markers associated with myeloid differentiation
Analyze the induction of apoptotic resistance markers in resistant cell lines
Amx-883 significantly increased expression of differentiation markers CD11b and CD86 in AML cell lines
Combination treatment with amx-883 and venetoclax demonstrated synergistic efficacy
Significant tumor reduction was observed in murine models treated with amx-883
Amx-883 prevented the emergence of resistance to venetoclax by inhibiting MCL-1 and BCL-2 expression