Petri, Laszlo; Egyed, Attila; Bajusz, David; Imre, Timea; Hetenyi, Anasztazia; Martinek, Tamas; Abranyi-Balogh, Peter; Keseru, Gyorgy M. published the artcile< An electrophilic warhead library for mapping the reactivity and accessibility of tractable cysteines in protein kinases>, Application of C19H34O2, the main research area is protein kinase inhibitor drug discovery; JAK3; Kinase cysteome profiling; MELK; Small-molecule kinase inhibitors; Targeted covalent inhibitors; Warhead selection.
Targeted covalent inhibitors represent a viable strategy to block protein kinases involved in different disease pathologies. Although a number of computational protocols have been published for identifying druggable cysteines, exptl. approaches are limited for mapping the reactivity and accessibility of these residues. Here, we present a ligand based approach using a toolbox of fragment-sized mols. with identical scaffold but equipped with diverse covalent warheads. Our library represents a unique opportunity for the efficient integration of warhead-optimization and target-validation into the covalent drug development process. Screening this probe kit against multiple kinases could exptl. characterize the accessibility and reactivity of the targeted cysteines and helped to identify suitable warheads for designed covalent inhibitors. The usefulness of this approach has been confirmed retrospectively on Janus kinase 3 (JAK3). Furthermore, representing a prospective validation, we identified Maternal embryonic leucine zipper kinase (MELK), as a tractable covalent target. Covalently labeling and biochem. inhibition of MELK would suggest an alternative covalent strategy for MELK inhibitor programs.
European Journal of Medicinal Chemistry published new progress about Drug discovery. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Application of C19H34O2.
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