Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 64, Issue 21, Pages 15608-15628Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.1c00574
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Funding
- Key Organics Ltd., UK
- OxStem Oncology
- MRC Molecular Haematology Unit grant [MC_UU_00016/6]
- MRC [MC_UU_00016/1, MC_UU_00016/6] Funding Source: UKRI
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A novel compound, OXS007417, identified through a phenotypic high-throughput screen, shows promise in decreasing tumor volume in acute myeloid leukemia.
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.
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