Abstract: The present invention includes novel compounds and methods for preventing or treating diseases associated with and/or caused by overexpression and/or uncontrolled activation of a tyrosine kinase in a subject in need thereof. In certain embodiments, the compounds of the present invention comprise a tyrosine kinase inhibitor, a linker and a ubiquitin ligase binder. The methods of the present invention comprise administering to the subject an pharmaceutically effective amount of at least one compound of the invention.

Abstract: The present invention provides bifunctional compounds that efficiently dephosphorylate certain phospho-activated target proteins. Such target proteins can be any protein involved in the pathway of a disease or disorder, such as but not limited to cancer, neurodegeneration, metabolic disease, diabetes, insulin resistance, and so forth.

Abstract: The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Abstract: The present invention includes novel compounds and methods for preventing or treating diseases associated with and/or caused by overexpression and/or uncontrolled activation of a tyrosine kinase in a subject in need thereof. In certain embodiments, the compounds of the present invention comprise a tyrosine kinase inhibitor, a linker and a ubiquitin ligase binder. The methods of the present invention comprise administering to the subject an pharmaceutically effective amount of at least one compound of the invention.

Abstract: The present invention includes novel compounds and methods for preventing or treating diseases associated with and/or caused by overexpression and/or uncontrolled activation of a tyrosine kinase in a subject in need thereof. In certain embodiments, the compounds of the present invention comprise a tyrosine kinase inhibitor, a linker and a ubiquitin ligase binder. The methods of the present invention comprise administering to the subject an pharmaceutically effective amount of at least one compound of the invention.

Abstract: The present invention includes novel compounds and methods for preventing or treating diseases associated with and/or caused by overexpression and/or uncontrolled activation of a tyrosine kinase in a subject in need thereof. In certain embodiments, the compounds of the present invention comprise a tyrosine kinase inhibitor, a linker and a ubiquitin ligase binder. The methods of the present invention comprise administering to the subject an pharmaceutically effective amount of at least one compound of the invention.

Abstract: The description relates to imide-based compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

Abstract: The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Abstract: The description relates to imide-based compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

Abstract: The present invention includes compounds that act as degraders of a target protein, wherein degradation is independent of the class of the target protein or its localization. In certain embodiments, the invention comprises a compound comprising a protein degradation moiety covalently bound to a linker, wherein the ClogP of the compound is equal to or higher than 1.5. In other embodiments, the target protein contemplated within the invention comprises a posttranslational modified protein or intracellular protein. In yet other embodiments, compounds of the present invention are used to treat disease states wherein protein degradation is a viable therapeutic approach, such as cancer or any sort of oxidative stress disease state.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsinlike activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: Described herein are therapeutic strategies (methods and compositions) useful for treating conditions in which cilia are affected and which manifest with cysts and/or fibrosis, such as conditions in which the kidney, pancreas, liver and/or spleen are affected and contain cysts. Particular embodiments described herein are therapeutic strategies in which PC-2 agonists, particularly agonists (calcium channel agonists) that target PC-2 directly and/or selectively, are administered to individuals with mutations in PKD1, in order to alter the course of polycystic kidney disease, particularly ADPKD. In specific embodiments, the invention relates to use of PC-2 agonists triptolide and triptolide derivatives to regulate calcium release. In other aspects, the invention relates to use of PC-2 agonists to treat or aid in the treatment of any condition in which a calcium channel, such as the gene product of PKD1 and/or PKD2, is mutated; calcium signaling is abnormal; or both.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: The present invention is based on the discovery of a composition that provides targeted ubiquitination. Specifically the composition contains a ubiquitin pathway protein binding moiety which recognizes a ubiquitin pathway protein and a targeting moiety which recognizes a target protein. In addition, the present invention provides libraries of compositions, where each composition contains a ubiquitin pathway protein binding moiety and a member of a molecular library. The libraries of the present invention can be used to identify proteins involved in a predetermined function of cells.

Abstract: The present invention is based on the discovery of a composition that provides targeted ubiquitination. Specifically the composition contains an ubiquitin pathway protein binding moiety which recognizes an ubiquitin pathway protein and a targeting moiety which recognizes a target protein. In addition, the present invention provides libraries of compositions, where each composition contains an ubiquitin pathway protein binding moiety and a member of a molecular library. The libraries of the present invention can be used to identify proteins involved in a predetermined function of cells.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: The present invention is based on the discovery of a composition that provides targeted ubiquitination. Specifically the composition contains a ubiquitin pathway protein binding moiety which recognizes a ubiquitin pathway protein and a targeting moiety which recognizes a target protein. In addition, the present invention provides libraries of compositions, where each composition contains a ubiquitin pathway protein binding moiety and a member of a molecular library. The libraries of the present invention can be used to identify proteins involved in a predetermined function of cells.

Abstract: The present invention is based on the discovery of a composition that provides targeted ubiquitination. Specifically the composition contains an ubiquitin pathway protein binding moiety which recognizes an ubiquitin pathway protein and a targeting moiety which recognizes a target protein. In addition, the present invention provides libraries of compositions, where each composition contains an ubiquitin pathway protein binding moiety and a member of a molecular library. The libraries of the present invention can be used to identify proteins involved in a predetermined function of cells.