Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia.
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ABSTRACT:
SUBMITTER: Lewis TA
PROVIDER: S-EPMC5150668 | biostudies-literature | 2016 Dec
REPOSITORIES: biostudies-literature
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Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia.
Lewis Timothy A TA Sykes David B DB Law Jason M JM Muñoz Benito B Rustiguel Joane K JK Nonato Maria Cristina MC Scadden David T DT Schreiber Stuart L SL
ACS medicinal chemistry letters 20160928 12
Homeobox transcription factor A9 (HoxA9) is overexpressed in 70% of patients diagnosed with acute myeloid leukemia (AML), whereas only a small subset of AML patients respond to current differentiation therapies. A cell line overexpressing HoxA9 was derived from the bone marrow of a lysozyme-GFP mouse. In this fashion, GFP served as an endogenous reporter of differentiation, permitting a high-throughput phenotypic screen against the MLPCN library. Two chemical scaffolds were optimized for activit ...[more]
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