Abstract: The present invention relates to compounds, compositions, and methods for treating diseases or conditions by modulating (e.g., reducing) the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C.

Abstract: The present invention relates to bifunctional compounds for targeted kinase degradation, methods for treating diseases or conditions mediated by aberrant kinase activity, and methods for identifying degradable kinases and optimal kinase:scaffold pairs.

Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions by modulating (e.g., reducing) the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C.

Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treat diseases or conditions mediated by aberrant activity of at least one class IIa histone deacetylase (HDAC4/5/7/9).

Abstract: Presented are methods of assessing the teratogenicity of agents by measuring the degradation of SALL4, and related compounds with reduced teratogenicity. Provided herein is a method for assessing the teratogenicity of an agent comprising: contacting an agent with SALL4; and measuring levels of SALL4, wherein the agent is teratogenic if SALL4 levels are substantially reduced in the presence of the agent relative to in the absence of the agent.

Abstract: Disclosed are bispecific compounds (degraders) that target cereblon (CRBN) for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds as research tools and to reduce adverse side effects associated with a cereblon targeted therapy.

Abstract: Disclosed are compounds and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof that may cause degradation of various proteins e.g., IKZF2 (Helios). Also disclosed are pharmaceutical compositions containing same, and methods of making and using the compounds to treat diseases and disorders associated with Helios and which may benefit from Helios degradation.

Abstract: The present invention relates to bispecific compounds, compositions, and methods for treating diseases or conditions mediated by aberrant histone deacety lase 6 (HDAC6) activity.

Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by aberrant histone deacetylase (HCADC) (e.g., HDAC3) activity.

Abstract: Described herein are compositions and methods for modulating protein abundance in a target-specific manner via degron tags.

Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by aberrant histone deacetylases 6 and 8 (HDAC6/8) activity.

Abstract: Disclosed are heterobifunctional compounds that effectuate selective degradation of a target protein, and which include a targeting ligand that binds a target protein and at least one other protein, a ligand that binds an E3 ubiquitin ligase or a component of E3 ubiquitin ligase, and a specificity modulating linker that links the first ligand and the second ligand. Pharmaceutical compositions containing the compounds, and methods of using and making the compounds are also disclosed.

Abstract: The invention features methods for characterizing a cancer as sensitive or resistant to Bcl6 therapies, as well as compositions and methods for inducing the degradation or polymerization of a polypeptide of interest.

Abstract: Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. The compounds described herein bind an E3 ubiquitin ligase (e.g., Cereblon) and induce degradation of a transcription factor (e.g., IKZF1, IKZF3). Also provided are pharmaceutical compositions comprising the compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases (e.g., cancers (e.g., carcinoma); leukemia, lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer, multiple myeloma, and acute myeloid leukemia (AML))). Further provided are methods of inducing the degradation of a transcription factor (e.g., IKZF1, IKZF3) by administering a compound or composition described herein to a subject and/or to a biological sample (e.g., cell or tissue).

Abstract: Disclosed are compositions and methods of treating cancers by constitutively activating protein phosphatase 2A (PP2A) without blocking signaling through the dopamine D2 receptor, that entail administering a therapeutically effective amount of an analog of perphenazine (PPZ) of formula (I) or (II), or a related PPZ analog lacking dopamine receptor D2 inhibitory activity, or a pharmaceutically acceptable salt thereof.

Abstract: Disclosed are bifunctional compounds (degraders) that target Wee1 tyrosine kinase for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.

Abstract: Disclosed are heterobifunctional compounds that effectuate selective degradation of a target protein, and which include a targeting ligand that binds a target protein and at least one other protein, a ligand that binds an E3 ubiquitin ligase or a component of E3 ubiquitin ligase, and a specificity modulating linker that links the first ligand and the second ligand. Pharmaceutical compositions containing the compounds, and methods of using and making the compounds are also disclosed.

Abstract: Presented are methods of assessing the teratogenicity of agents by measuring the degradation of SALL4, and related compounds with reduced teratogenicity. Provided herein is a method for assessing the teratogenicity of an agent comprising: contacting an agent with SALL4; and measuring levels of SALL4, wherein the agent is teratogenic if SALL4 levels are substantially reduced in the presence of the agent relative to in the absence of the agent.

Abstract: A stencil for cutting sandpaper and it is formed from a sheet of plastic transparent plastic material having four corner lips extending down from the corners of the sheet. These corner lips have inner edges that define a rectangular recess for receiving a stack of standard sized sheets of sandpaper. Linear slots and arcuate slots in the stencil allow the sandpaper to be cut into two equal parts, three equal parts, four equal parts or circular disks having 6, 7, and 8 inch diameters.

Abstract: An auxiliary paint brush bucket that has a planar front wall, an arcuate rear wall and a bottom wall to form an open top container. The front surface of the front wall has a plurality of conical shaped raised bumps thereon formed in a predetermined pattern so that a paint roller may be squeezed against the front wall surface to remove excess paint and it runs down the channels between the respective bumps. A unique pair of laterally spaced clips are formed on the top edge of the rear wall so that it can be removably installed along the inner surface of either a two gallon or five gallon paint bucket.