Abstract: The present disclosure relates to compounds that are Syk inhibitors or pharmaceutically acceptable salts or co-crystals thereof, and pharmaceutical compositions thereof, and to their use in the treatment of various disease states, including cancer and inflammatory conditions.

Abstract: This disclosure is directed, at least in part, to GPR40 agonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the GPR40 agonists are gut-restricted compounds. In some embodiments, the GPR40 agonists are full agonists or partial agonists. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.

Abstract: The present disclosure provides [1,2,4]triazolo[4,3-b][1,2,4]triazine, [1,2,4] triazolo[4,3-b]pyridazine, and [1,2,3]triazolo[4,5-b]pyrazine derivatives, and pharmaceutically acceptable salts, solvates or prodrugs thereof, as tyrosine kinase c-MET inhibitors, which are useful as novel anticancer and/or anti-inflammatory agents.

Abstract: The present invention features compositions including sepiapterin, or a pharmaceutically acceptable salt thereof, and methods for the treatment of BH4-related disorders. In some embodiments, these compositions and methods result in an increase in plasma exposure of BH4.

Abstract: The present invention derives from the unexpected finding that ADRA2a antagonists decrease fibrosis in non-alcoholic fatty liver disease (NAFLD). Thus, by antagonising ADRA2a, many of the unwanted consequences or symptoms of NAFLD, may be reduced, such as impaired cognitive activity and fibrosis progression. The present invention utilises these findings to identify and provide ADRA2a antagonists that may be used in the treatment of fibrosis in NAFLD.

Abstract: The invention relates to crystalline folate salts. The salt consists of a folate anion and an organic cation. The folate anion is 5-methyl-(6S)-tetrahydrofolic acid, and the cation is an organic compound which is an alkanolamine selected from the group consisting of choline, N-methylaminoethanol, 2-amino-2-methylpropanol and 2-dimethylaminoethanol.

Abstract: The present application provides methods of treating a disease, such as Pompe disease, in a subject, comprising detecting an erythropoiesis biomarker in a sample of the subject after administration of methotrexate and a therapeutic agent to the subject, and administering further treatment with or without concurrently administering additional immune tolerance induction or immunosuppression therapy based on the level of the erythropoiesis biomarker. Further provided by the present application are methods and kits for assessing the level of immune tolerance to a therapeutic agent in a subject based on detection of an erythropoiesis biomarker after administration of methotrexate and the therapeutic agent to the subject.

Abstract: The present disclosure provides imidazolyl compounds of Formula (I) and methods of preparing the compounds. The provided compounds are able to bind protein kinases and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase in a subject or cell and/or in treating or preventing a disease (e.g., proliferative disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.

Abstract: Provided herein, among other things, is a method of treating a cancer patient without the need for a tissue biopsy. In some embodiments, the method may comprise (a) performing or having performed a sequencing assay on cell-free DNA (cfDNA) from a sample of blood from the patient to determine if the cell-free DNA comprises actionable and/or non-actionable sequence variations in one or more target genes, and (b) treating the patient using the following method: i. administering a therapy that is targeted to an actionable sequence variation if the patient is identified as having the actionable sequence variation, and ii. administering a non-targeted therapy in the absence of any follow-up genetic testing on DNA extracted from a tissue biopsy if one or more non-actionable sequence variations and no actionable sequence variations are identified.

Abstract: Provided are compounds of formula (I): or a cosmeceutically acceptable or pharmaceutically acceptable salts thereof. Additionally provided are pharmaceutical and/or cosmeceutical compositions and formulations comprising the compounds and/or the cosmeceutically acceptable or pharmaceutically acceptable salts thereof, therapeutic and/or cosmetic methods using same for modulating (e.g., inhibiting) CREB binding protein (CBP)/?-catenin mediated signaling in treating skin related diseases, conditions or disorders (e.g., dermatitis, psoriasis, scarring, alopecia, etc.) mediated by aberrant CBP/?-catenin signaling, and cosmetic methods for treating skin conditions (e.g., aging, etc.) mediated by aberrant CBP/?-catenin signaling.

Abstract: The present invention provides stable, pharmaceutically acceptable and ophthalmologically suitable compositions comprising therapeutically effective amounts of both a pilocarpine compound and a brimonidine compound for treating an ocular condition, the compositions comprising a low amount of sodium chloride present in a limited ratio with the active pharmaceutical ingredient(s). In certain embodiments, provided compositions are free of both a borate buffer and a citrate buffer. Compositions provided by the invention surprisingly demonstrate pharmaceutically acceptable stability characteristics when stored under controlled room temperature conditions for an extended period of time. Further, the invention provides methods of manufacturing such compositions in both liquid (solution) and gel form, and methods of their use in treating ocular conditions, such as presbyopia.

Abstract: The present invention is directed to methods for improving night vision and visual performance in low light conditions comprising ophthalmological administration of compositions comprising low dose brimonidine and a vehicle for improved performance.

Abstract: Solid forms of the compound, 6-(6-aminopyrazin-2-yl)-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)imidazo[1,2-a]pyrazin-8-amine, and solid forms of salts or co-crystals of Compound I, were prepared and characterized: Also provided are processes of making the solid forms and methods of use thereof.

Abstract: The present invention is directed to, in part, fused heteroaryl compounds of Formula (III-II): and compositions thereof, useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

Abstract: An apparatus, and method, for building a longevity profile, the apparatus including at least a processor and a memory communicatively connected to the at least a processor, the memory containing instructions configuring the at least a processor to receive longevity measurement data of a user, where the longevity measurement data includes at least a transcriptomic datum. The processor further configured to determine at least a longevity hallmark as a function of the longevity measurement data and generate a longevity profile of the user of the user as a function of a longevity machine-learning model, wherein the longevity machine-learning model receives the at least a longevity hallmark and the longevity measurement as inputs and outputs the longevity profile, and transmit the longevity profile to an output device.

Abstract: Described herein are somatostatin subtype-2 receptor (SST2R) targeted therapeutics that target tumor cells expressing SST2R and their use in the treatment of cancer.

Abstract: The present invention relates to a novel AUTOTAC chimeric compound in which a new p62 ligand and a target-binding ligand are connected by a linker, a stereoisomer, hydrate, solvate or prodrug thereof, and a pharmaceutical or food composition for the prevention or treatment of diseases by degrading the target protein including the same as an active ingredient. They can target specific proteins to adjust their concentrations, and can also deliver drugs and other small molecule compounds to lysosomes. The AUTOTAC chimeric compound according to the present invention can be usefully used as a pharmaceutical composition for the prevention, amelioration or treatment of various diseases by selectively eliminating specific proteins.

Abstract: The present disclosure relates to crystalline forms of 8-(2-fluorobenzyl)-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazine, depicted below as a compound of Formula (I): which are useful as a stimulator of soluble guanylate cyclase (sGC). The present disclosure also provides pharmaceutically acceptable compositions comprising the crystalline forms and methods of using said compositions in the treatment of various disorders.

Abstract: Polymorphs of a bis-mesylate salt of a compound of Formula IA: are provided. Also provided are process for making the polymorphs and methods of use thereof.

Abstract: The invention discloses novel RAR gamma selective agonists used in the treatment of cancer. The invention also discloses administration of RAR gamma selective agonists to mammals, including humans for the purpose of selectively activating RAR gamma receptor and treat cancer by way of activating tumor infiltrating lymphocytes.

Abstract: Disclosed herein are WD40 repeat domain protein 5 (WDR5) degradation/disruption compounds including a WDR5 ligand, a degradation/disruption tag, and a linker, and methods of using such compounds in the treatment of WDR5-mediated diseases.

Abstract: The present disclosure is directed to methods of treating fibrotic conditions and inflammation by administration of TR? agonists. The disclosure provides methods wherein the abnormal deposition of extracellular matrix components, such as collagen, keratin, or elastin, is reduced, either through interaction of TR? agonists with TGF-?-dependent inflammatory pathways, or by other mechanisms, thereby ameliorating fibrotic symptoms.

Abstract: A process for preparing a diazabicyclooctane compound represented by the following formula (I): wherein A represents RcO—; B represents NH or NC1-6 alkyl; C represents a benzyl group; Rc represents a C1-6 alkyl group; A is substituted with one substituent Fn1, wherein Fn1 represents an azetidine group; the process including: (a) silylating the compound represented by the following formula (IV-c): wherein in the formula (IV-c), OBn represents benzyloxy, and (b) carrying out an intramolecular urea formation reaction.

Abstract: Abuse deterrent solid dosage formulations containing 5-({[2-Amino-3-(4-carbamoyl-2,6 -dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy -benzoic acid, and processes for the preparation and administration of these formulations.

Abstract: The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, the treatment of ischemic injury, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, infections of the skin, peripheral vascular disease, stroke, asthma, and the like.

Abstract: Provided herein are substituted tetrazolo[1,5-a]pyrazines and tetrazolo[1,5-c]pyrimidines useful for the treatment of diseases and disorders associated with the adenosine receptor, such as cancer. Also provided herein are pharmaceutical compositions, methods of inhibiting the activity of an adenosine receptor, and methods of treating disease and disorders using these compounds.

Abstract: Disclosed are compounds of Formula (I) to (VIII): or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R3 is a bicyclic heteroaryl group substituted with zero to 3 R3a; and R1, R2, R3a, R4, and n are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmaceutical compositions comprising such compounds. These compounds are useful in inhibiting or preventing platelet aggregation, and are useful for the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder.

Abstract: The application relates to inhibitors of USP1 useful in the treatment of cancers, and other USP1 associated diseases and disorders, having the Formula: where R1, R2, R3, R3?, R4, R5, X1, X2, X3, X4, and n are described herein.

Abstract: A method for treating pancreatic cancer in a subject in need thereof comprising, administering to the subject an effective amount of a tubulin polymerization inhibitor compound is described herein. More particularly, a method for treating pancreatic ductal adenocarcinoma in a subject in need thereof comprising, administering to the subject an effective amount of a substituted reverse pyrimidine tubulin polymerization inhibitor compound alone or in combination with other chemo-therapeutic agents is described herein.

Abstract: The present invention relates to compounds and pharmaceutical composition having antiviral effects. Over 1200 molecules were screened and 55 molecules having statistically significant anti-HIV activity were identified and selected. The compound Methotrexate (MTX-HYD) and its analogues, the combinations thereof and their combination with other anti-retrovirals were selected for repurposing the compounds as anti-HIV drugs. The present invention may further relate to pharmaceutical composition comprising compounds in combination with active drugs having anti-HIV activity.

Abstract: The present invention generally relates to various compounds that are useful as ?-synuclein ligands. The invention further relates to methods of using these compounds and their radiolabeled analogs for the detection of synucleinopathies, including Parkinson's disease (PD).

Abstract: A prophylactic or therapeutic agent for spinal muscular atrophy according to the present invention includes a compound represented by the formula (I) or a salt thereof: the variables are described herein.

Abstract: Bruton's tyrosine kinase (Btk) inhibitors have the following Formula (I):

Abstract: The present invention provides relatively low pH, stable, pharmaceutically acceptable and ophthalmologically suitable compositions comprising effective amounts of pilocarpine and brimonidine compounds for treating an ocular condition, wherein compositions demonstrate a significant difference in the amount or rate of one or more pharmaceutical ingredient(s) absorbed or retained by ocular tissue or compared to reference composition(s) with similar compositional characteristics but having a significantly higher pH. In aspects compositions are characterizable by other elements, e.g., the inclusion of benzalkonium chloride, a limited amount of sodium chloride, or both. In embodiments, compositions are free of both a borate and a citrate buffer. Compositions provided by the invention surprisingly demonstrate pharmaceutically acceptable stability when stored under controlled room temperature conditions for an extended period of time.

Abstract: The present disclosure provides a compound represented by structural Formula (I): or a pharmaceutically acceptable salt thereof useful for treating a cancer.

Abstract: This invention relates to compounds for treating acute myeloid leukemia or inhibiting recurrence of acute myeloid leukemia and for inhibiting growth of and/or killing leukemic stem cells.

Abstract: The present disclosure relates to synthesizing and utilizing fluorescent dye compounds or pharmaceutically acceptable salts thereof. Conjugation of amino acid groups to the fluorescent dyes increase specificity and detection of the compound. Methods of manufacture and synthesis of the compounds for use thereof in diagnostic imaging are contemplated.

Abstract: The present disclosure describes methods of treating a central nervous system condition associated with oxidative stress using a 5-lipoxigenase activating protein (FLAP) inhibitor, for example, N-acetylcysteine or nordihydroguaiaretic acid. The present disclosure also describes methods of treating a central nervous system condition with N-acetylcysteine and a second therapeutic agent such as prostaglandin E2.

Abstract: Compounds that inhibit KRas G12D. In particular, compounds that inhibit the activity of KRas G12D, pharmaceutical compositions comprising the compounds and methods of use therefor, and in particular, methods of treating cancer. The compounds have a general structure represented by Formula (I): or a pharmaceutically acceptable salt thereof.

Abstract: The present disclosure relates generally to eukaryotic initiation factor 2B modulators, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or prodrug thereof, and methods of making and using thereof.

Abstract: The present disclosure relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, particularly anticancer agents such as prednisone, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

Abstract: Provided are compounds of Formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2A, R2B, R3, R4, and R5 are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof. Also provided are methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

Abstract: This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize) the apelin receptor (also referred to herein as the APJ receptor; gene symbol APLNR). This disclosure also features compositions containing the same as well as other methods of using and making the same. The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which a decrease in APJ receptor activity (e.g., repressed or impaired APJ receptor signaling; e.g., repressed or impaired apelin-APJ receptor signaling) or downregulation of endogenous apelin contributes to the pathology and/or symptoms and/or progression of the disease, disorder, or condition.

Abstract: The present invention provides a method of treating heart failure with reduced ejection fraction, by administering to a patient at risk of such damage, a pharmaceutically effective amount of a composition which inhibits the anchoring of PP2A to mAKAP?. This composition is preferably in the form of a viral based gene therapy vector that encodes a fragment of mAKAP? to which PP2A binds.

Abstract: The present disclosure provides a compound represented by structural Formula (I): or a pharmaceutically acceptable salt thereof useful for treating a cancer.

Abstract: The invention relates to a computer-implemented Bayesian inference method for performing Bayesian inference in a Bayesian network, which includes a continuous child node (3) and its discrete parent node (2) having two states. Being provided with a calibrated continuous probability distribution of the observations of the child node (3) for each of the two states of the parent node (2), the inferring for a new observation of the child node (3) for which the state of the parent node (2) is not known of the probability of at least a first state of the parent node (2) makes use of masses of portions of the probability distributions that depend on a locational relationship of the probability distributions and the value of the new observation. This may ensure that the inferred probability of the first state of the parent node (2) monotonically changes with monotonically changing values of the new observation.

Abstract: Disclosed herein are WD40 repeat domain protein 5 (WDR5) degradation/disruption compounds including a WDR5 ligand, a degradation/disruption tag, and a linker, and methods of using such compounds in the treatment of WDR5-mediated diseases.

Abstract: A method of measuring immunocompetence is described. This method provides a means for assessing the effects of diseases or conditions that compromise the immune system and of therapies aimed to reconstitute it. This method is based on quantifying T-cell diversity by calculating the number of diverse T-cell receptor (TCR) beta chain variable regions from blood cells.

Abstract: An apparatus for extending longevity, wherein the apparatus includes at least a processor and a memory communicatively connected to the at least a processor. The memory containing instructions configuring at least a processor to receive a longevity measurement pertaining to a user. The memory containing instructions further configuring the processor to select a target longevity factor as a function of the longevity measurement and then identify a longevity treatment plan as a function of the target longevity factor. The memory containing instructions further configuring the processor to generate a longevity treatment protocol as a function of the longevity treatment and the longevity measurement.

Abstract: The present application belongs to the field of pharmaceutical chemistry, and relates to a furo[3,4-b]pyrrole-containing BTK inhibitor, and in particular, to a compound of formula (I), a stereisomer or pharmacologically acceptable salt thereof, a preparation method therefor, a pharmaceutical composition containing the compound, and use thereof in treating BTK-related diseases.