Abstract
Phosphoinositide-3-kinase δ (PI3Kδ) is a critical regulator of cell growth and transformation and has been explored as a therapeutic target for a range of diseases. Through the exploration of the thienopyrimidine scaffold, we have identified a ligand-efficient methylation that leads to remarkable selectivity for PI3Kδ over the closely related isoforms. Interrogation through the Free-Wilson analysis highlights the innate selectivity the thienopyrimidine scaffold has for PI3Kδ and provides a predictive model for the activity against the PI3K isoforms.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amines / chemistry
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Humans
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Isoenzymes / chemistry
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Isoenzymes / metabolism
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Methylation
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Nitrogen / chemistry
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Phosphatidylinositol 3-Kinases / chemistry
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphoinositide-3 Kinase Inhibitors / chemical synthesis
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Phosphoinositide-3 Kinase Inhibitors / chemistry*
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Phosphoinositide-3 Kinase Inhibitors / pharmacology*
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Pyrimidines / chemistry
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Serum Albumin, Human / metabolism
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Structure-Activity Relationship*
Substances
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Amines
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Isoenzymes
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Phosphoinositide-3 Kinase Inhibitors
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Pyrimidines
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2-aminopyrimidine
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Nitrogen
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Serum Albumin, Human