Abstract: The present invention provides compounds or their pharmaceutically acceptable salts and their pharmaceutical compositions that can be administered to a host such as a human in need thereof for the treatment of a disorder, such as cancer, mediated by mutant BRAF. The compounds efficiently degrade Class I, II and III mutant BRAF proteins.

Abstract: The present invention provides selected glutarimides which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and alter the substrate specificity of the CRBN E3 ubiquitin ligase complex, resulting in breakdown of intrinsic downstream proteins. The disclosed compounds are useful for the treatment of cancer.

Abstract: This invention provides Degronimers that have carbon-linked E3 Ubiquitin Ligase targeting moieties (Degrons), which can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.

Abstract: The invention provides for the treatment of mutant epidermal growth factor receptor (EGFR) mediated cancer that has metastasized to the brain or other area of the central nervous system with a compound that degrades a mutant form of EGFR via the ubiquitination of the EGFR protein and subsequent proteasomal degradation. The invention also provides advantageous drug combinations for the treatment of such cancer that include a compound herein that degrades a mutant form of EGFR in combination with a second anti-cancer agent.

Abstract: The present invention provides selected dihydrobenzimidazolones which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and alter the substrate specificity of the CRBN E3 ubiquitin ligase complex, resulting in breakdown of intrinsic downstream proteins. The disclosed compounds are useful for the treatment of cancer.

Abstract: The invention provides compounds that degrade the epidermal growth factor receptor (EGFR) including mutant forms via the ubiquitination of the EGFR protein and subsequent proteasomal degradation. The compounds are useful for the treatment of various cancers.

Abstract: BRD9 protein degradation compounds or pharmaceutically acceptable salts thereof are provided for the treatment of disorders mediated by BRD9, including but not limited to abnormal cellular proliferation.

Abstract: The present invention provides compounds and intermediates. The present invention also provides compounds which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and their use for the treatment of abnormal cellular proliferation. The present invention also provides compounds that may be used as synthetic intermediates in the synthesis of bifunctional compounds used for targeted protein degradation.

Abstract: The present invention provides compounds which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and their use for the treatment of abnormal cellular proliferation. The present invention also provides compounds that may be used as synthetic intermediates in the synthesis of bifunctional compounds used for targeted protein degradation.

Abstract: Heterobifunctional compounds for targeted protein degradation that include a tricyclic cereblon binder linked to an appropriate protein targeting ligand to degrade a targeted disease-mediating protein of interest are provided.

Abstract: There is provided a method of forming cutting blades using selective laser melting comprising positioning a first part of an elongate strip (30) with pre-formed teeth (32) within a powder bed (20), forming coating layers layer-by-layer to create a cutting surface on each pre-formed tooth by repeatedly depositing a layer of powder on the powder bed and scanning a laser beam over the deposited powder to fuse powder to the pre-formed teeth.

Abstract: Pharmaceutical Degraders and Degrons for use in therapeutic applications are described herein.

Abstract: The present invention provides selected glutarimides which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and alter the substrate specificity of the CRBN E3 ubiquitin ligase complex, resulting in breakdown of intrinsic downstream proteins. The disclosed compounds are useful for the treatment of cancer.

Abstract: Tricyclic compounds that degrade IKZF2 and/or IKZF4 are provided for medical therapy, including abnormal cellular proliferation, including cancer, inflammatory disorders, neurodegenerative disorders or autoimmune disorders.

Abstract: There is provided a powder feeder (10, 10?) comprising a main chamber (12, 12?) with a gas inlet (14, 14?) and a powder outlet (16), at least one secondary chamber (20, 20?) configured to receive powder and a shaver element (22, 40, 50), wherein the shaver element (22, 40, 50) is positioned directly above an opening (26, 26?) in the at least one secondary chamber (20, 20?). The secondary chamber (20, 20?) further comprises a piston (28, 28?) movable towards the shaver element (22, 40, 50) so as to urge powder upwards. Examples of a shaver element include a rotatable screw (22), a conveyor belt (40) and a rotating disc (50) with protrusions (54).

Abstract: The present invention provides selected dihydrobenzimidazolones which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and alter the substrate specificity of the CRBN E3 ubiquitin ligase complex, resulting in breakdown of intrinsic downstream proteins. The disclosed compounds are useful for the treatment of cancer.

Abstract: The invention provides cereblon binders of Formulas: or pharmaceutically acceptable salts thereof, for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway along with their use in therapeutic applications to treat medical disorders including, but not limited to cancer.

Abstract: This invention provides Degronimers that have E3 Ubiquitin Ligase targeting moieties (Degrons) that can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation. The invention also provides Degrons that can be used to treat disorders mediated by cereblon or an Ikaros family protein, and methods of use and compositions thereof as well as methods for their preparation.

Abstract: Novel compounds which act as protein degradation inducing moieties for proto-oncogene tyrosine-protein kinase receptor (RET), which may be either wild type RET or a mutant form of RET.

Abstract: A BRD9 protein degrading compound of structure or a pharmaceutically acceptable salt thereof is provided for the treatment of a disorder mediated by BRD9, including but not limited to abnormal cellular proliferation including cancer.