Discovery of GBA-16-24 as a highly potent, selective ATR inhibitor for the treatment of FLT3-mutated acute myeloid leukemia - PubMed
3 hours ago
- #ATR inhibitor
- #FLT3-mutated AML
- #synthetic lethality
- Discovery of GBA-16-24, a highly potent and selective ATR inhibitor.
- GBA-16-24 developed via a ring-opening strategy, suitable for prodrugs or PROTACs.
- Identified FLT3 as a potential synthetic lethal target for GBA-16-24.
- GBA-16-24 more effectively inhibits cell proliferation in FLT3-mutated AML compared to FLT3-wild-type AML.
- GBA-16-24 disrupts the cell cycle and induces apoptosis in MV-4-11 cells.
- Synergistic anti-AML effects observed when combined with clinically approved FLT3 inhibitors.
- Proposes combination of ATR and FLT3 inhibition as a novel synthetic lethal strategy for FLT3-mutated AML.