Abstract: The specification relates to compounds of Formula (I): and to pharmaceutically acceptable salts thereof, to processes and intermediates used for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of diseases such as liver disease.

Abstract: Provided are biomarkers for predicting the efficacy of MDM2 inhibitor or Bcl-2/Bcl-xL dual inhibitors or Bcl-2 inhibitor or Bcl-xL inhibitor in treating cancer patients. Also provided are compositions, e.g., kits, for evaluating gene levels of the biomarkers and methods of using such gene levels to predict a cancer patient's response to the MDM2 inhibitors or Bcl-2/Bcl-xL dual inhibitors or Bcl-2 inhibitor or Bcl-xL inhibitor. Such information can be used in determining prognosis and treatment options for cancer patients.

Abstract: The present disclosure provides compounds and pharmaceutically acceptable salt thereof, and methods of using the same. The compounds and methods have a range of utilities as therapeutics, diagnostics, and research tools. In particular, the subject compositions and methods are useful for reducing signaling output of oncogenic proteins.

Abstract: Disclosed are compounds that activate excitatory amino acid transporter 2 (EAAT2), as well as methods of using these compounds to treat or preventing diseases, disorders, and conditions associated with glutamate excitotoxicity.

Abstract: The present disclosure provides compounds that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.

Abstract: The present invention relates to pyrrolo[1,2-b]-2-pyridazinone compounds of formula (I), or their isotopic forms, stereoisomers, or pharmaceutically acceptable salts thereof as 5-HT4 receptor agonists. The present invention also describes methods of making such compounds, pharmaceutical compositions comprising such compounds, and their use in the treatment of gastrointestinal disease or disorder.

Abstract: Methods are provided for modulating MRGPR X2 generally, or for treating a MRGPR X2 or a MRGPR X2 ortholog dependent condition, more specifically, by contacting the MRGPR X2 or the MRGPR X2 ortholog by administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I): or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein W, Z, R1, R2, R3, R4, R5, R6 and Rx are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Abstract: The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.

Abstract: Disclosed are compounds of following formula (I): in which all symbols have the same meanings as the definitions described in the specification; or a salt thereof. The compounds or a salt thereof are useful as a prophylactic and/or therapeutic agent for cancer, Huntington's disease, Alzheimer's disease and the like.

Abstract: Disclosed herein are compounds and methods of treating diseases and/or conditions associated with FGFR inhibition.

Abstract: The present disclosure provides compounds which are useful for a number of catalytic transformations of organic molecules, non-limiting examples including dehydrogenation of alkanes. The present disclosure further relates to methods of preparing the compounds of the present disclosure.

Abstract: The present invention relates to compounds and methods useful as inhibitors of phosphodiesterase 4 (PDE4) for the treatment or prevention of inflammatory diseases and other diseases involving elevated levels of cytokines and proinflammatory mediators.

Abstract: The present disclosure provides CDK9 inhibitors. Also provided are methods of treating a disease or a disorder comprising administering to a subject in need of treatment one of the CDK9 inhibitors disclosed herein. In some embodiments, the disease or disorder to be treated is cancer. In some embodiments, the disease or disorder is liver cancer.

Abstract: Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R1, R2, R3, R4, R6, R7, R8 and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

Abstract: Described herein is a process for the preparation of a compound of Formula I, wherein R1 and R2 each have the meanings provided in the description. Also described is a process for the preparation of pharmaceutically-active compounds including the process for the preparation of compounds of Formula I.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates, hydrates, tautomers or stereoisomers thereof, wherein R1, R2, R2a, R3, Ra2, Ra4, Ra5, Ra6, Ra7, X1, X1a, A1 and A2 have the meaning as indicated in the description and claims. The invention further relates to pharmaceutical compositions comprising said compounds, their use as medicament and in a method for treating and preventing of one or more diseases or disorders associated with integrated stress response.

Abstract: The present invention provides stapled polypeptides of the Formulae (I) and (VI): and salts thereof; wherein the groups ; R1a, R1b, R1c, R2a, R3a, R2b, R3b, R4a, R4b, RA, RZ, L1a, L1b, L2, L3, XAA, v, w, p, m, s, n, t, and q are as defined herein. The present invention further provides methods of preparing the inventive stapled polypeptides from unstapled polypeptide precursors. The present invention further provides pharmaceutical compositions comprising a stapled polypeptide of Formula (I) or (VI), and methods of using the stapled peptides. The present invention also provides modifications of the staples post ring closing metathesis.

Abstract: The invention discloses use of miloxacin in the preparation of medicines for treating and/or preventing diseases with T-type calcium channel as a therapeutic target. The invention discloses new use of miloxacin, which provides a new theoretical and technical support for developing medicines for treating and/or preventing diseases with T-type calcium channel as a therapeutic target, thus having a broad prospect of application in the field of clinical treatment.

Abstract: Substituted pyridazinone compounds, conjugates, and pharmaceutical compositions for use in the treatment of neuromuscular diseases, such as Duchenne Muscular Dystrophy (DMD), are disclosed herein. The disclosed compounds are useful, among other things, in the treating of DMD and modulating inflammatory inhibitors IL-1, IL-6 or TNF-?.