Selective covalent inhibition of kinases by targeting poorly conserved cysteines has proven highly fruitful to date in the development of chemical probes and approved drugs. However, this approach is limited to ∼200 kinases possessing such a cysteine near the ATP-binding pocket. Herein, we report a novel approach to achieve selective, irreversible kinase inhibition, by targeting the conserved catalytic lysine residue. We have illustrated our approach by developing selective, covalent PI3Kδ inhibitors that exhibit nanomolar potency in cellular assays, and a duration of action >48 h in CD4+ T cells. Despite conservation of the lysine residue throughout the kinome, the lead compound shows high levels of selectivity over a selection of lipid an...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Selective covalent inhibition of kinases by targeting poorly conserved cysteines has proven highly f...
Previously held under moratorium in Chemistry department (GSK) from 12th April 2018 until 18 June 20...
Previously held under moratorium in Chemistry department (GSK) from 12th April 2018 until 18 June 20...
Covalent inhibition is a powerful strategy to develop potent and selective small molecule kinase inh...
Targeted covalent inhibitor design is gaining increasing interest and acceptance. A typical covalent...
Protein kinases are a large family of approximately 530 highly conserved enzymes that transfer a γ-p...
The expansion of the target landscape of covalent inhibitors requires the engagement of nucleophiles...
Covalent inhibitors have numerous applications as drugs, as tools for drug discovery, and as probes ...
Protein kinases are a large family of approximately 530 highly conserved enzymes that transfer a γ-p...
Kinase inhibitors have experienced a dramatic evolution over the last two decades, as multi-targeted...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Selective covalent inhibition of kinases by targeting poorly conserved cysteines has proven highly f...
Previously held under moratorium in Chemistry department (GSK) from 12th April 2018 until 18 June 20...
Previously held under moratorium in Chemistry department (GSK) from 12th April 2018 until 18 June 20...
Covalent inhibition is a powerful strategy to develop potent and selective small molecule kinase inh...
Targeted covalent inhibitor design is gaining increasing interest and acceptance. A typical covalent...
Protein kinases are a large family of approximately 530 highly conserved enzymes that transfer a γ-p...
The expansion of the target landscape of covalent inhibitors requires the engagement of nucleophiles...
Covalent inhibitors have numerous applications as drugs, as tools for drug discovery, and as probes ...
Protein kinases are a large family of approximately 530 highly conserved enzymes that transfer a γ-p...
Kinase inhibitors have experienced a dramatic evolution over the last two decades, as multi-targeted...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...
Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) h...