Reata Pharmaceuticals, Inc.
CYSTEINE-DEPENDENT INVERSE AGONISTS OF NUCLEAR RECEPTORS ROR-GAMMA/ROR-GAMMA-T AND METHODS OF TREATING DISEASES OR DISORDERS THEREWITH

Abstract:

Provided herein are compounds, compositions and methods for treating and preventing diseases and disorders, comprising administering to patients therapeutically effective amounts of cysteine-dependent inverse agonists of the nuclear receptor ROR.gamma./ROR.gamma.t. In some such embodiments, the inverse agonists bind to cysteine 476 of a nuclear receptor ROR.gamma. in the patient. Also provided are methods, as well as compounds and compositions, for modulating the activity of ROR.gamma. and ROR.gamma.t by binding to the allosteric binding site through a covalent bond. In some aspects, the present disclosure relates to using compounds containing Michael acceptor groups which bind to a cysteine residue in the allosteric binding site such as cysteine 476 in ROR.gamma..