Induction of differentiation is a promising therapeutic strategy against acute myeloid leukemia. However, current differentiation therapies are effective only to specific patient populations. To identify novel differentiation agents with wider efficacy, we developed a phenotypic high-throughput screen with a range of genetically diverse cell lines. From the resulting hits, one chemical scaffold was optimized in terms of activity and physicochemical properties to yield OXS007417, a proof-of-concept tool compound, which was also able to decrease tumor volume in a murine in vivo xenograft model.
Journal article
2021-11-11T00:00:00+00:00
64
15608 - 15628
20
Animals, Antineoplastic Agents, Cell Differentiation, Cell Survival, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Female, Humans, Leukemia, Myeloid, Acute, Male, Mice, Mice, Inbred NOD, Mice, SCID, Molecular Structure, Neoplasms, Experimental, Phenotype, Structure-Activity Relationship, Tumor Cells, Cultured