5 results about "Glucocorticoid receptor" patented technology

Methods and compositions for treating a subject with adrenocortical carcinoma and hypercortisolism are disclosed. The methods result in a reduction in ACC tumor burden, restoration of T cell signaling pathways and natural killer (NK) cell signaling pathways, increased infiltration of T cells and NK cells into ACC tumors, and decreased infiltration of neutrophils into ACC tumors, among other therapeutic effects. The methods include administering a glucocorticoid receptor modulator (GRM) (which may be a selective glucocorticoid receptor modulator (SGRM)) and an antibody checkpoint inhibitor. In some embodiments, the GRM (e.g., the SGRM) is administered orally. The GRM may be a non-steroidal compound containing a fused azadecalin structure; a heteroaryl ketone-fused azadecalin structure; or an octahydro-fused azadecalin structure.

The present invention provides a method for preparing pyrimidine cyclohexylglucocorticoid receptor modulators, a method for preparing intermediates of pyrimidine cyclohexylglucocorticoid receptor modulators, and thioether compounds.

Disclosed herein are antibody-drug-conjugates (ADC) that allow for delivery and release of glucocorticoid receptor modulators into desired tissues. The disclosed ADCs include a peptide that facilitates the release of a glucocorticoid receptor modulator by legumain. The antibody-drug-conjugates are useful as therapeutic agents for treating various autoimmune disorders, inflammatory disorders, and blood cancers. Pharmaceutical compositions which include the ADCs are also disclosed, as are methods of treating autoimmune disorders, inflammatory disorders, and blood cancers by administering a therapeutically effective amount of an antibody-drug-conjugate disclosed herein under conditions effective to treat said disorders.

Methods and compositions for treating a subject suffering from adrenocortical carcinoma and having excess cortisol are disclosed. The methods provide therapeutic benefits including reduction of ACC tumor load, restoration of T-cell and natural killer (NK) cell signaling pathways, increase in T-cell and NK cell infiltration into the ACC tumor, reduction of neutrophil infiltration into the ACC tumor in the patient, and other therapeutic benefits. The methods include administration of a glucocorticoid receptor modulator (GRM) (which may be a selective glucocorticoid receptor modulator (SGRM)) and an antibody checkpoint inhibitor. In embodiments, the GRM (e.g., a SGRM) is orally administered. The GRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.

Disclosed herein are antibody-drug-conjugates (ADC) that allow for delivery and release of glucocorticoid receptor modulators into desired tissues. The disclosed ADCs include a peptide that facilitates the release of a glucocorticoid receptor modulator by legumain. The antibody-drug-conjugates are useful as therapeutic agents for treating various autoimmune disorders, inflammatory disorders, and blood cancers. Pharmaceutical compositions which include the ADCs are also disclosed, as are methods of treating autoimmune disorders, inflammatory disorders, and blood cancers by administering a therapeutically effective amount of an antibody-drug-conjugate disclosed herein under conditions effective to treat said disorders.