This invention relates to small-molecule compounds that are potential therapeutics for Acute Myeloid Leukemia (AML), specifically AML with the FMS-like tyrosine kinase 3 (FLT3) mutation. The compounds also show activity versus Abl kinases, platelet-derived growth factor receptor (PDGFR), and the dual-specificity tyrosine regulated/Cdc2-like (DYRK/CLK) family of kinases, well-known targets for anti-cancer therapeutics. These compounds could be used in conjunction with the current AML therapeutic standard of care Gilteritinib, or as a standalone therapeutic, especially for patients that have developed resistance to Gilteritinib. Background: Acute myeloid leukemia (AML) is a type of cancer that affects the blood and begins in the bone marrow, rapidly spreading into the bloodstream. It can sometimes extend to other areas of the body, such as the lymph nodes, liver, spleen, brain, spinal cord, and testicles. Among AML subtypes, FLT3 mutations are among the most frequent genetic alterations, occurring in about 25–35% of adult AML cases. These mutations confer an adverse prognosis, including higher relapse rates and shorter overall survival. Gilteritinib is the most widely used therapy for relapsed/refractory FLT3-mutated AML, but patients can develop drug resistance through mechanisms such as new FLT3 gene mutations or bypassing signaling pathways. This invention can be a potential second-line treatment to Gilteritinib for AML, for patients who have developed resistance to the Gilteritinib. Applications:
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