5 results about "Cereblon" patented technology

This disclosure relates, in one aspect, to substituted N-(2-(2,6-dioxopiperidinyl-3-yl)-1,3-dioxoisoindoline-5-yl)arylsulfonamide analogs used as modulators of cereblon (CRBN) activity, methods for their preparation, pharmaceutical compositions comprising the same, and methods of using the same to treat various clinical conditions and diseases, such as uncontrolled cell proliferation diseases that may be associated with cereblon protein dysfunction and / or GSPT1 dysfunction, such as cancer. In various further aspects, the disclosed compounds can selectively modulate the degradation of the GSPT1 protein, i.e., the disclosed compounds can act as GSPT1 degrading agents. This abstract is intended as a scanning tool for searching in a particular field and is not intended to limit the scope of this disclosure.

Provided herein are bifunctional compounds with a moiety (e.g., lenalidomide, thalidomide) that is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and another moiety that is a binder of a target protein (e.g., kinase (e.g., CDK (e.g., CDK9 and / or CDK12))) to induce degradation of the target protein CDK9 and / or CDK12. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and / or preventing diseases (e.g., proliferative diseases, such as cancers (e.g., ovarian cancer, breast cancer, or prostate cancer))). Provided also are methods of inducing the degradation of the target protein (e.g., kinase (e.g., CDK (e.g., CDK9 and / or CDK12))), and methods of inducing apoptosis in a cell in a biological sample or subject by administering the bifunctional compound or composition described herein.

Certain Androgen receptor PROTAC (PROteolysis TArgeting Chimera) compounds contain a series of 2,4-dioxotetrahydropyrimidinyl derivatives that bind cereblon. The PROTAC compounds may be viewed as being comprised of an androgen receptor binding moieties, a linker and a cereblon binding moiety or degron. Medical uses of these PROTAC compounds are also disclosed.