ONO-7475 + venetoclax

ONO-7475 is a highly specific small molecule inhibitor of the receptor tyrosine kinases AXL and MERTK, developed by Ono Pharmaceutical. It disrupts survival and proliferation pathways in acute myeloid leukemia (AML) cells, including inhibition of ERK1/2 phosphorylation and reduction of anti-apoptotic protein MCL1 expression. Venetoclax (ABT-199), marketed as Venclexta, is a B-cell lymphoma 2 (BCL2) inhibitor that induces apoptosis in cancer cells by blocking BCL2. The combination of ONO-7475 with venetoclax has shown potent synergistic activity against FLT3-mutant AML cell lines and primary cells, including those resistant to venetoclax due to MCL1 overexpression. This combination targets both the BCL2 pathway and compensatory survival mechanisms mediated by AXL/MERTK signaling, offering a promising therapeutic strategy for relapsed or refractory AML[1][2][3][4].

Other names

tamnorzatinib + venetoclax