Abstract: Provided herein are bifunctional compounds that bind a target protein (e.g., a selected protein) and/or induce ubiquitination for degradation of the target protein. In particular, provided are compounds that bind a bromodomain or bromodomain-containing protein (e.g., BET proteins) or histone methyltransferases (HMTs, e.g., enhancer of zeste homolog 1 (EZH1), or FKBP12) and can promote its degradation by recruiting it to the ubiquitin receptor RPN13 (e.g., RA190), for proteasomal degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating and/or preventing diseases (e.g., proliferative diseases, cancers, benign neoplasms, pathological angiogenesis, inflammatory diseases, and autoimmune diseases) and musculoskeletal diseases, and methods of inducing the degradation of a target (e.g., a target protein) by recruiting it to the ubiquitin receptor RPN13 of the proteasome in a subject by administering a compound or composition described herein.

Abstract: The present application provides bifunctional compounds of Formula (X): or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for Bruton's tyrosine kinase (BTK). The present application also relates to methods for the targeted degradation of BTK through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BTK which can be utilized in the treatment of disorders modulated by BTK.

Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., HCK, BTK, LYN) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating diseases (e.g., proliferative diseases) in a subject in need thereof).

Abstract: The present invention relates to a homogeneous, time resolved, Förster resonance energy transfer (TR-FRET)-based method for detection of SARS-CoV-2, SARS CoV-1, and MERS-CoV antibodies in a patient fluid sample.

Abstract: Disclosed are to compounds, compositions, and methods for treating diseases or conditions mediated by aberrant serine-arginine protein kinase (SRPK) 1 and SRPK2 activity.

Abstract: Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.

Abstract: The present application relates to mass spectrometry methods for use in identifying proteins or other biomolecules which are bound irreversibly by test compounds.

Abstract: Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.

Abstract: Disclosed are compounds with immunomodulatory activity, methods of making the compounds, pharmaceutical compositions containing the compounds, and methods of using the compounds to treat diseases or disorders characterized or mediated by dysfunctional protein activity.

Abstract: The present invention relates to compounds, compositions and methods for treating diseases or conditions mediated by proteins of the SWI/SNF chromatin-remodeling complex, including PB1.

Abstract: The present invention provides dihydrooxydiazinone compounds of general formula (I) in which R1, R2, R3, and R4, are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative diseases, as a sole agent or in combination with other active ingredients.

Abstract: Provided herein, in some embodiments, are methods, compositions and kits for large-scale production of long single-stranded DNA in solution.

Abstract: The invention provides methods and compositions for inducing brown fat cell differentiation through modulation of both Prdm16 and C/EBP? activity and/or expression. Also provided are methods for preventing or treating obesity or an obesity related disorder in a subject through stimulation of both Prdm16 and C/EBP? expression and/or activity. Further provided are methods for identifying compounds that are capable of modulating both Prdm16 and C/EBP? expression and/or activity.

Abstract: Described and featured herein are antagonistic biparatopic antibodies that specifically bind and inhibit an FGF receptor (e.g., FGFR2) and methods of using such antibodies for the treatment of cancers, including Cholangiocarcinoma (CCAs).

Abstract: The present invention relates to gene expression signatures that predict response and resistance to targeted therapy and immunotherapy.

Abstract: As described below, the present invention features compositions, panels of biomarkers, and methods for characterizing chronic lymphocytic leukemia (CLL) for prognosis and selection of a subject for a treatment and/or inclusion in a clinical trial.

Abstract: The present invention provides circularized RNA and methods of making, purifying, and using same.

Abstract: Devices, systems, and methods for efficiently preparing and containing a small volume of liquid target material for irradiation by a cyclotron are provided. In various embodiments, a device includes a housing having a chamber and the housing has a top surface that is substantially flat. The chamber has a substantially flat base and a wall having a first portion extending from the base with a first radius of curvature and a second portion extending from the first portion having a second radius of curvature that is less than the first radius. The chamber also includes an inlet aperture, an outlet aperture, and a lip having a second surface that is substantially flat and recessed from the first surface. In various embodiments, the device includes a heat sink including a plurality of parallel fins disposed around the chamber.

Abstract: The present invention relates, in part, to methods of treating a cancer in a subject comprising administering to the subject a therapeutically effective amount of an agent that inhibits one or more biomarkers listed in Table 1 in combination with an immunotherapy.

Abstract: Diagnostic assays for facilitating the diagnosis of lymphoplasmacytic lymphoma (LPL) are provided. The method comprises assessing a biological sample of the subject for the presence of a mutation at position 38182641 in chromosome 3p22.2, wherein presence of the mutation is indicative that the subject has LPL. Also, provided are targeted therapies, methods for monitoring the progression or recurrence of LPL, and a sensitive and inexpensive real-time allele specific polymerase chain reaction assay for reliable and quantitative assessments of the mutation.