Abstract: The present application relates to compounds comprising an ester, a thioester, or a hydrazide moiety and methods of synthesizing these compounds. The present application also relates to pharmaceutical compositions containing the compounds and methods of treating cell proliferative disorders mediated by the Hedgehog (Hh) signaling pathway, such as cancer, by administering the compounds and pharmaceutical compositions to subjects in need thereof.

Abstract: An isolated nucleic acid molecule encoding a mutant MEK1 protein having MEK1 activity is disclosed. The mutant MEK1 protein comprises an amino acid substitution at position 121 of wild-type MEK1 shown in SEQ ID NO: 2. The amino acid substitution confers resistance to one or more RAF or MEK inhibitors on a cell expressing the mutant MEK1 protein.

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: The present invention provides novel compounds of Formulae (I?) 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: DCAF15 is a substrate recognition (adaptor) protein of E3 ubiquitin ligase. Disclosed herein are compounds that recruit ubiquitin ligase CRL4DCAF15, to a target RNA recognition motif (RRM), causing its degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.

Abstract: The present invention relates to methods for identifying, assessing, preventing, and treating cancer (e.g., head, neck, and/or lung cancers in humans). A variety of PD-L1 isoform biomarkers are provided, wherein alterations in the copy number of one or more of the biomarkers and/or alterations in the amount, structure, and/or activity of one or more of the biomarkers is associated with cancer status and indicates amenability to treatment or prevention by modulating PD-1 and/or PD-L1 levels.

Abstract: The application relates to a compound of Formula (I): which modulates the activity of TRIM33, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which TRIM33 plays a role.

Abstract: A method for autonomously identifying symptom terms in free running text data includes the acts of defining a plurality of symptom terms associated with a particular pathology or therapeutic substance or procedure, labeling in a text data set any defined symptom terms and associating a tag indicating any of a positive, negative, or other status with relation to the labeled symptom term, and processing with a natural language processing algorithm multiple different subsets of the text data containing labeled symptom terms to identify a frequency of occurrence of a symptom term and to improve identification accuracy.

Abstract: A shielding apparatus for a radioisotope production system is provided. The shielding apparatus is capable of being retro-fitted to the housing of preinstalled radioisotope production systems. The shielding apparatus comprises a plurality of shield layers removably stacked on top of a base that is mounted to the top of the housing via spacers defining space or air gap between the base and housing. The shield layers and base are positioned above and extending between the interface between moveable shields and a moveable base of the radioisotope production system, such that the shielding apparatus is positioned within the trajectory of a radioisotope production system beam.

Abstract: The present invention generally relates to a controlled fluidic device to develop spatially complex environments to enhance the rate of evolution in cell populations. The method further provides an enhanced understanding in the emergence, for example, drug resistance during cancer chemotherapy.

Abstract: The invention provides compositions and methods useful in characterizing and/or treating classical Hodgkin's Lymphoma and/or primary mediastinal B-cell lymphoma (PMBL). In embodiments, the characterization is carried out using a biological sample comprising circulating tumor DNA (ctDNA) from a subject.

Abstract: The disclosure provides a powerful new approach to dual-strand high-throughput next-generation sequencing that improves upon duplex sequencing. The method provides a novel multi-oligonucleotide adapter construct that is ligated to DNA fragments to be sequenced (e.g., genomic DNA fragments) library construction method that concatenates both strands of each DNA duplex into a linear sequence. By physically linking both strands, the products are self-sufficient to form duplex consensus. This strategy has the potential to provide 1,000-fold more accurate sequencing with minimal added cost, and could directly enhance existing products (WGS, WES, targeted panels) offered at the Genomics Platform.

Abstract: The present disclosure provides compositions and methods for the treatment of PPARG activated cancer. For example, the present disclosure provides PPARG signaling modulators for the treatment of bladder cancer. In particular, therapeutic and/or prophylactic compositions and uses of PPARG inverse-agonists are described.

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: Disclosed are compounds and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or 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: Disclosed herein are methods to improve the efficiency of absolute quantification of nucleic acid targets such as digital PCR and digital isothermal amplification, and/or reduce the amount of nucleic acid sample required to determine the absolute quantity of target sequences in the sample.

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 invention relates, in part, to methods of treating a subject afflicted with a cancer comprising administering to the subject a therapeutically effective amount of an agent that inhibits or promotes the copy number, the expression level, and/or the activity of one or more biomarkers listed in Table 1 or a fragment thereof. Also provided herein are methods of detecting ADAR1 or ISG15 dependency in a high proliferation cell (e.g., a cancer cell). Also provided are methods of detected increased interferon signaling pathway activity in a high proliferation cell (e.g., a cancer cell). Included herein are methods of treating cancer with inhibitors of ADAR1 or ISG15. Methods of screening for such inhibitors are also provided herein. Methods of identifying the likelihood of a cancer to be responsive to an ADAR1 inhibitor are also provided.

Abstract: Provided herein are Stimulator of Interferon Genes (STING) and Stimulated 3 Prime Antisense Retroviral Coding Sequences (SPARCS) genes as biomarkers for determining an effective therapy for treating cancer. Further provided are methods for treating cancer using said biomarkers.

Abstract: The present invention provides methods of treating cancer by combination therapy with CDK4/6 inhibitors and immune checkpoint inhibition.