Selective Glucocorticoid Receptor Properties of GSK866 Analogs with Cysteine Reactive Warheads.

ABSTRACT: Synthetic glucocorticoids (GC) are the mainstay therapy for treatment of acute and chronic inflammatory disorders. Due to the high adverse effects associated with long-term use, GC pharmacology has focused since the nineties on more selective GC ligand-binding strategies, classified as selective glucocorticoid receptor (GR) agonists (SEGRAs) or selective glucocorticoid receptor modulators (SEGRMs). In the current study, GSK866 analogs with electrophilic covalent-binding warheads were developed with potential SEGRA properties to improve their clinical safety profile for long-lasting topical skin disease applications. Since the off-rate of a covalently binding drug is negligible compared to that of a non-covalent drug, its therapeutic effects can be prolonged and typically, smaller doses of

SUBMITTER: Chirumamilla CS 

PROVIDER: S-EPMC5672024 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature