Abstract: Disclosed are bispecific compounds (degraders) that target ITK or a zinc finger (ZnF) protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat diseases and disorders characterized or mediated by ITK or ZnF protein activity.

Abstract: Disclosed are bispecific compounds (degraders) that target ?-synuclein protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat neurodegenerative diseases.

Abstract: 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 (e.g., RA190) that is a binder of the ubiquitin receptor RPN13 to induce degradation of RPN13 and thereby inhibit proteasome function. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, cancers, benign neoplasms, pathological angiogenesis, inflammatory diseases, and autoimmune diseases). Provided also are methods of inducing the degradation of ubiquitin receptor RPN13 by administering a bifunctional compound or composition described herein, wherein one component of the bifunctional compound is a binder of an E3 ubiquitin ligase (e.g., lenalidomide, thalidomide) and another component of the compound is a binder of ubiquitin receptor RPN13 (e.g., RA190) in a subject.

Abstract: The present disclosure provides a method of treating a subject having a cancer. The method comprises reducing expression of a Carm 1 gene and/or a Carm 1 effector gene in a cell of the subject, and/or reducing activity of a Carm 1 protein and/or a Carm 1 effector protein in a cell of the subject. The cancer is resistant to immunotherapy and/or checkpoint blockade treatment.

Abstract: Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the disclosed compounds or compositions for treating and/or preventing diseases (e.g., inflammatory diseases, neurological diseases (e.g., Alzheimer's disease), infectious diseases (e.g., viral infections (e.g., infections caused by viral human hepatitis (e.g., hepatitis B), a flaviviridae family virus (e.g., a flavivims (e.g., Zika virus)))), and proliferative diseases (e.g., cancer (e.g., lung cancer, prostate cancer, skin cancer, thyroid cancer, pancreatic cancer, colorectal cancer, liver cancer, leukemia, or lymphoma)) in a subject. Provided are methods of inhibiting a protein kinase (e.g., MAP2K (e.g., MKK7)) in a subject. Also provided are methods of inhibiting MKK7 in a subject in need thereof.

Abstract: The disclosure provides novel methods, compositions, and kits that combine hybrid capture using short allele-specific probes with duplex molecular” barcoding and noise modeling within each sample to afford high accuracy sequencing of rare mutations at low cost.

Abstract: The present invention is based on the identification of novel biomarkers predictive of endocrine resistance in breast cancer.

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: Provided herein are compounds of (I-A), (I-B), or (II), and pharmaceutically acceptable salts, solvates, hydrates, poly-morphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are methods, uses, and kits involving the inventive compounds and pharmaceutical compositions thereof for treating and/or preventing diseases (e.g., proliferative diseases (e.g., cancers), inflammatory diseases (e.g., fibrosis), autoimmune diseases (e.g., sclerosis)) in a subject. Provided are methods of inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) and/or inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD)) in a subject.

Abstract: The present invention provides novel compounds of Formula (I), (II), or (III), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g.

Abstract: The disclosure is directed to compositions and methods that are useful for the treatment of a neoplasia. Specifically, methods for inducing cell death or reducing cell survival of a neoplastic cell (e.g., rhabomyosarcoma) and methods of treating a subject having a neoplasia characterized by a loss of VPS4 expression are disclosed.

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., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) 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 a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: The present invention is based in part on the identification of DPH1 and other members of the diphthamide synthesis pathway as biomarkers of resistance to an ADP-ribosylating toxin in a cell, and methods for identification, assessment, and treatment of a condition that is resistant to an ADP-ribosylating toxin.

Abstract: The application relates to a compound having Formula (I): which modulates the activity of EGFR, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which EGFR plays a role.

Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. The compounds described herein are used as enhancers and/or modifiers of an immune response (e.g., innate and/or adaptive immune response), and are useful in treating and/or preventing a disease, as adjuvants in a vaccine for the disease, (e.g., proliferative disease, inflammatory disease, autoimmune disease, infectious disease, or chronic disease), or as stand alone anti-infective or immune response modifying agents. Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.

Abstract: The present invention is based, in part, on the discovery of galectin 1 (Gal1) epitopes against which anti-Gal1 agents can neutralize Gal1 function, as well as anti-Gal1 agents and methods useful for neutralizing Gal1 function.

Abstract: Extended field-of-view imaging is enabled by combined imaging with a kilovolt (“kV”) x-ray source and a megavolt (“MV”) x-ray source, in which at least one of the corresponding x-ray detectors is laterally offset from the target isocenter by an amount such that the x-ray detector does not have a view of the target isocenter. This scan geometry enables the reconstruction of non-truncated images without resorting to the more expensive solution of outfitting the imaging or radiotherapy system with enlarged x-ray detectors.

Abstract: The present disclosure provides combination therapy comprising a BET inhibitor and a protein phosphatase 2A (PP2A) activator, a B-cell lymphoma-2 (Bcl-2) inhibitor, a B-cell lymphoma-extra large (Bcl-xl) inhibitor, a casein kinase 2 (CK2) inhibitor, and/or a mediator complex subunit 1 (MED1) for cancer. The combination therapy is expected to be synergistic in treating the cancer, compared to the monotherapy. Methods for identifying a subject having a cancer that is resistant to or at risk of developing resistance to bromodomain and extra terminal (BET) inhibitor therapy are also provided.

Abstract: Disclosed are bispecific compounds (degraders) that target ALK or ALK and FAK for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the bispecific compounds to treat diseases and disorders characterized or mediated by aberrant ALK or ALK and FAK activity.

Abstract: Disclosed are to bifunctional compounds that target PRMT5 for degradation, compositions, and methods for treating diseases or conditions mediated by aberrant arginine methyltransferase 5 (PRMT5) activity.