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- W2413667427 abstract "We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable of inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse bone marrow. Kinome profiling versus more than 300 kinases in vitro and cellular selectivity assessments demonstrate that 11 has similar subnanomolar activity against Flt3, an additional important target in acute myelogenous leukemia (AML), with pharmacologically useful selectivity versus other kinases examined." @default.
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- W2413667427 date "2014-08-06" @default.
- W2413667427 modified "2023-10-15" @default.
- W2413667427 title "<b>UNC2025</b>, a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor" @default.
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- W2413667427 doi "https://doi.org/10.1021/jm500749d" @default.
- W2413667427 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4148167" @default.
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