Abstract: The present disclosure features methods and compositions for treating amyotrophic lateral sclerosis (ALS). The disclosed methods comprise administering to a subject having or suspected of having ALS a hematopoietic stem progenitor cell expressing at least one neuroprotective agent. The compositions disclosed comprise hematopoietic stem progenitor cells transduced to express a neuroprotective agent.

Abstract: Presently described are compositions and methods for performing genome-wide enrichment of DNA microsatellites (e.g., homopolymers) containing deletions and facilitating their detection via sequencing or other downstream methodologies. Additionally, disclosed herein are compositions and methods for selecting the genomic fraction containing poly-adenine/poly-thymidine homopolymer repeats and other A:T-rich sequences of low melting temperature from the genome, so that very little sequencing is required to detect the enriched homo-polymer deletions.

Abstract: Disclosed are bispecific compounds (degraders) that target CDK7 for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.

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: 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: The present invention provides methods of increasing the efficiency of genome editing.

Abstract: The present invention is based, in part, on the discovery of monoclonal antibodies, and antigen-binding fragments thereof, that specifically bind to MICA/B ?3 domain, as well as immunoglobulins, polypeptides, nucleic acids thereof, and methods of using such antibodies for diagnostic, prognostic, and therapeutic purposes.

Abstract: Provided are compositions for use in methods for treating diseases associated with expression of mesothelin comprising administering a cell that expresses a chimeric antigen receptor (CAR) specific to mesothelin in combination with a PD-L1 inhibitor.

Abstract: The disclosure relates to methods for treating cancers (e.g., cancers having a BRCA1 and/or BRCA2 mutation(s)) by administering to the subject an effective amount of a ubiquitin-specific protease 1 (USP1) inhibitor.

Abstract: The present disclosure provides nucleic acid-based nanoswitch catenanes and methods of use. A nanoswitch catenane may include a single-stranded nucleic acid comprising a first and second terminal domain linked to each other to form a host ring by one of a first, second or third switchable bridges, wherein the first switchable bridge is formed in the presence of a reaction agent through the reaction of two cognate functional groups, each linked to a terminal domain of the single-stranded nucleic acid, wherein the second switchable bridge is formed in the presence of a biomolecule of interest through binding of the bio-molecule of interest to two cognate antibodies, each linked to a terminal domain of the single stranded nucleic acid, and wherein the third switchable bridge is a link between two cognate functional groups that breaks in the presence of a dissociation agent. A nanoswitch catenane may also include a circular nucleic acid guest ring catenated with the host ring.

Abstract: The present invention provides compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) are binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.

Abstract: Disclosed are compounds that possess inhibitory activity against FAK. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds to treat cancer mediated by aberrant FAK activity.

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 bispecific compounds (degraders) that target EP300/CBP for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.

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 relates to compositions and methods for treating early T-cell precursor acute lymphoblastic leukemia (ETP T-ALL).

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: Disclosed are bifunctional compounds comprising a GDC-0068 analog that binds AKT isoforms AKT1, 2 and 3, pharmaceutical compositions, and methods for treating diseases or conditions mediated by dysfunctional AKT activity.

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 that is a binder of a target protein (e.g., kinase (e.g., CDK (e.g., CDK9 and/or CDK12))) to induce degradation of the target protein CDK9 and/or CDK12. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, such as cancers (e.g., ovarian cancer, breast cancer, or prostate cancer))). Provided also are methods of inducing the degradation of the target protein (e.g., kinase (e.g., CDK (e.g., CDK9 and/or CDK12))), and methods of inducing apoptosis in a cell in a biological sample or subject by administering the bifunctional compound or composition described herein.

Abstract: Provided by the invention are methods for identifying therapeutic agents for treating multiple myeloma or another hematological malignancy, as well as methods for determining the prognosis of a patient with multiple myeloma or another hematological malignancy. The methods are based in part on the inventors' discovery that an extracellular form of cyclophilin A binds to CD147 expressed on multiple myeloma cells.