Abstract: A method for treating inflammation and/or autoimmune diseases comprises administering to a subject in need thereof, a composition comprising a CDK8 inhibitor. In another aspect, a method for increasing IL-10 production comprises administering to a subject in need thereof a CDK8 inhibitor. In another aspect, a method for enhancing Treg cell differentiation, comprising administering a composition comprising a CDK8 inhibitor. In certain example embodiments, the subject suffers from an inflammatory bowel disease. In certain other example embodiments, the subject requires immunosuppression to prevent rejection following a transplantation procedure.

Abstract: The present disclosure provides methods of increasing skin pigmentation in a subject in need thereof using salt-inducible kinase (SIK) inhibitors, such as macrocyclic compounds of Formula (I), bicyclic urea compounds of Formula (II), (III), and (IV), and compounds of Formula (V), (VI), (VI-A), or (VII). Also provided are pharmaceutical compositions, methods, and uses that include or involve a compound described herein.

Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of EGLN1-dependent cancers. In particular, the instant disclosure provides for identification of a cancer as EGLN1-dependent, and selection and/or administration of an inhibitor of EGLN1 or VHL (Von Hippel-Lindau Tumor Suppressor) as a therapeutic agent for such a cancer and/or subject having or at risk of developing such a cancer.

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 compounds of the present disclosure are inhibitors of kinases (e.g., a cyclin-dependent kinase (CDK) (e.g., CDK7)). The compounds may be selective for inhibiting the activity of a kinase (e.g., CDK7) over certain other kinases (e.g., CDK2, CDK9, CDK12). Also provided are pharmaceutical compositions, kits, methods of use, and uses that involve the compounds. The compounds may be useful in inhibiting the activity of a kinase, down-regulating the transcription of MYC or MCL-1, inhibiting the growth of a cell, inducing apoptosis of a cell, treating a disease, and/or preventing a disease (e.g., proliferative disease, cystic fibrosis).

Abstract: Disclosed is a dTAG system comprising a small molecule degraders of FKBP12-tagged proteins via recruitment of Von Hippel-Lindau E3 ubiquitin ligase (VHL) E3 ubiquitin ligase and uses thereof.

Abstract: The invention provides methods to monitor cell free nucleic acids.

Abstract: Compounds of the present application or pharmaceutically acceptable salts thereof are provided and methods involving compounds of the present application as effective inhibitors of NEK are also provided.

Abstract: The present invention features improved methods of identifying patients having cancer (e.g., melanoma, adenocarcinoma, lung, cervical, liver or breast cancer) using biomarkers (e.g., PDE3A, SLFN12) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., DNMDP, zardaverine, and anagrelide).

Abstract: Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopologues, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing diseases (e.g., proliferative diseases (e.g., cancers and benign neoplasms), inflammatory diseases (e.g., rheumatoid arthritis), and vascular diseases (e.g., atherosclerosis) in a subject. Provided are methods of inhibiting a INK (e.g., JNK1, JNK2, or JNK3) in a subject.

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: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers that exhibit elevated expression and/or amplification of the ABCB1 (MDR1) transporter, optionally for reasons related to development of chemotherapeutic resistance having occurred during treatment with an initial chemotherapeutic drug. In particular, the instant disclosure provides for identification of a cancer as possessing elevated ABCB1 expression and/or exhibiting resistance to a non-tepoxalin chemotherapeutic drug, and selecting and/or administering tepoxalin, a tepoxalin derivative and/or metabolite thereof as a therapeutic agent for such a cancer and/or subject having or at risk of developing such a cancer. Methods and compositions for therapies that combine such tepoxalin or tepoxalin-related compounds with other cancer therapies and/or chemotherapeutic agents are also provided.

Abstract: The present disclosure provides methods of modulating regulatory T-cell activity and function.

Abstract: The present invention is based, in part, on the identification of novel human anti-PD-1, PD-L1, and PD-L2 antibodies. Accordingly, the invention relates to compositions and methods for diagnosing, prognosing, and treating conditions that would benefit from modulating PD-1, PD-L1, and/or PD-L2 activity (e.g., persistent infections diseases, autoimmune diseases, asthma, transplant rejection, inflammatory disorders and tumors) using the novel human anti-PD-1, PD-L1, and PD-L2 antibodies described herein.

Abstract: The present invention provides novel compounds of Formulae (I?), (I), (II?), and (II), 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 present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of proteinopathies, particularly MUC1-associated kidney disease (ADTKD-MUC1 or MKD), Retinitis Pigmentosa (e.g., due to rhodopsin mutations), autosomal dominant tubulo-interstitial kidney disease due to UMOD mutation(s) (ADTKD-UMOD), and other forms of toxic proteinopathies resulting from mutant protein accumulation in the ER or other secretory pathway compartments and/or vesicles, among others. The disclosure also identifies and provides TMED9-binding agents as capable of treating or preventing proteinopathies of the secretory pathway, and further provides methods for identifying additional TMED9-binding agents.

Abstract: Provided herein, in some embodiments, are methods, compositions and kits for controlling nucleation and assembly of molecular nanostructures, microstructures and macrostructures.

Abstract: The present disclosure provides novel heteroaryl compounds of formula (IV). Such compounds are useful for the treatment of cancers.

Abstract: The present invention is directed to antibodies binding to MUC1-C/extracellular domain (MUC1-C/ECD) and methods of using such antibodies to treat cancers that express the MUC1 antigen.

Abstract: Provided herein are bifunctional compounds with a moiety or domain that is a binder of the ubiquitin receptor RPN13 and another moiety or domain that is a binder of a target protein DOT1L to induce degradation of DOT1L. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, such as cancers). Provided also are methods of inducing the degradation of DOT1L by administering a bifunctional compound or composition described herein, wherein one domain of the bifunctional compound is a binder of the ubiquitin receptor RPN13 and another domain of the compound is a binder of the target protein DOT1L in a subject.

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.