Abstract: This invention is directed to novel carbocyclic prolinamide derivatives of Formula (I), and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of age-related macular degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry-AMD, wet-AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention.

Abstract: Compounds having activity as inhibitors of LRRK2 kinase are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R1a, R1b, R2, and L are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of LRRK2 kinase are also provided.

Abstract: Provided herein are aggregation-induced emission luminogens useful as photodynamic therapy and imaging agents, compositions including two or more aggregation-induced emission luminogens, pharmaceutical compositions comprising the same, and methods of use and preparation thereof.

Abstract: Compounds of Formula I that inhibit the activity of the diacylglycerol acyltransferase 2 (DGAT2) and their uses in the treatment of diseases linked thereto in animals are described herein.

Abstract: Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.

Abstract: Described herein are compounds having the following structure: formula (I) or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof. Also disclosed are compositions containing the compounds, methods of inhibiting activity of DYRK1 A in a cell, methods of increasing cell proliferation in a population of pancreatic beta cells, methods of treating a subject for a condition associated with insufficient insulin secretion, and methods of treating a subject for a neurological disorder.

Abstract: The invention relates to bicyclic heterocycle compounds of formula (I): or tautomeric or stereochemically isomeric forms, N-oxides, pharmaceutically acceptable salts or the solvates thereof; wherein R1, R2a, R2b, R3a, R3b, R5, R6, R7, R8, R9, p and E are as defined herein; to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Abstract: Compounds are provided that are useful as immunomodulators. The compounds have the Formula (I) including stereoisomers and pharmaceutically acceptable salts thereof, wherein R2a, R2b, R3, R3a, R4, R6, R7, R8, A, Z, X1 and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Abstract: Disclosed are compounds of Formula (I): or a salt thereof, wherein: R1, R2, R3, and R4 are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGK ?) and diacylglycerol kinase zeta (DGK?), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.

Abstract: Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for treating cancers. Specific cancers include those that are mediated by YAP/TAZ or those that are modulated by the interaction between YAP/TAZ and TEAD.

Abstract: The present application provides dihydropyrido[2,3-d]pyrimidone inhibitors of cyclin-dependent kinase 2 (CDK2), as well as pharmaceutical compositions thereof, and methods of treating cancer using the same.

Abstract: The present application belongs to the field of medicine. In particular, the present application relates to a diarylthiohydantoin compound as an androgen receptor antagonist or a pharmaceutically acceptable salt thereof, a preparation method of the same, a pharmaceutical composition comprising the compound, and a use thereof in treating a cell proliferative disease mediated by androgen. The compound of the present application has good antagonistic effect on androgen receptor and exhibits excellent antitumor effect.

Abstract: This application relates to processes and intermediates for the preparation of the PD-1/PD-L1 inhibitor (R)-1-((7-cyano-2-(3?-((2-(difluoromethyl)-7-((3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-yl)amino)-2,2?-dimethyl-[1,1?-biphenyl]-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carboxylic acid, and salts and crystalline forms thereof, where the PD-1/PD-L1 inhibitor and solid forms and salt forms thereof are useful in the treatment of various diseases including infectious diseases and cancer.

Abstract: Disclosed are compounds of Formula (I?), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.

Abstract: Provided are a compound of the formula: (5-(2-(4-((3,5-difluoro-4-(trifluoromethoxy)benzyl)amino)butoxy)ethoxy)benzo[c][2,6]naphthyridine-8-carboxylic acid) or a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising the above compound, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

Abstract: Novel 1,2-dioxo-2,3-dihydro-1H-pyrrolo[2,3-c]quinoline-7-carboxylic acid compounds, a method of synthesizing these compounds, a pharmaceutical composition comprising these compounds and a suitable carrier, and a method of using the compounds. The 1,2-dioxo-2,3-dihydro-1H-pyrrolo[2,3-c]quinoline-7-carboxylic acid compounds, identified as CK2 inhibitors, are useful as anticancer and/or antitumor agents, and as agents for treating other kinase-associated conditions including inflammation, pain, and certain immunological disorders, and other types of diseases such as diabetes, viral infection, neurodegenerative diseases.

Abstract: Generally, the present invention provides novel quinolone and 5H-1,5,7,11b-tetraaza-benzo[c]fluoren-6-one compounds and pharmaceutical composition thereof which may inhibit cell proliferation and/or induce cell apoptosis. The present invention also provides methods of preparing such compounds and compositions, and methods of making and using the same.

Abstract: The present invention is directed to, in part, fused heteroaryl compounds and compositions 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: Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are compounds useful for the treatment of various parasitic diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compostions, veterinary compositions and may be used in methods of treatment and/or prophylaxis of diseases spread by parasites, including malaria and cryptosporidiosis.

Abstract: The present invention relates to compounds useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

Abstract: The present invention relates to a method for separating an optically active hydroxy cineole derivatives by lixiviation and crystallization and enantiomerically pure optically active hydroxy cineole derivatives of purity greater than 99.5% that have been prepared by this process. The present invention further relates to use of the desired enantiomer having enantiomeric excess of at least 99.5% ee as prepared according to the present invention, for the synthesis of enantiomerically pure 7-oxabicyclo[2.2.1]heptane derivatives.

Abstract: The present invention provides a compound having the structure:

Abstract: The present invention relates to novel substituted dihydrothienopyrimidines with phosphodiesterase inhibitory activity, as well as to their use as therapeutic agents in the treatment of inflammatory diseases and conditions.

Abstract: The disclosure provides at least one entity chosen from compounds of Formula I, a tautomer thereof, a deuterated derivative of that compound or tautomer, and a pharmaceutically acceptable salt of any of the foregoing, compositions comprising the same, and methods of using the same, including uses in treating APOL1-mediated diseases, including pancreatic cancer, focal segmental glomerulosclerosis (FSGS), and/or non-diabetic kidney disease (NDKD).

Abstract: A method to convert asphaltenes to partially oxidized asphaltenes comprising the steps of treating the reactor feed in a tubular reactor to produce a reactor effluent, introducing the reactor effluent to a disengagement zone of a vessel reactor, introducing an oxidizing agent stream to the asphaltene collection zone of the vessel reactor, reacting the asphaltenes in the asphaltene-rich fraction with oxygen from the oxidizing agent, withdrawing a bottom reactor effluent from the asphaltene collection zone, reducing a temperature of the bottom reactor effluent to produce a cooled bottom effluent, reducing a pressure of the cooled bottom effluent in a pressure regulator unit to produce a centrifuge feed, separating the centrifuge feed in a centrifuge to produce a centrate, mixing the centrate and the upper upgraded stream in a product mixer to produce a mixed upgraded stream, and separating the mixed upgraded stream in a three-phase separator.

Abstract: The present invention relates to: a novel method for preparing a heterocyclic derivative compound of chemical formula I below; a novel intermediate compound used in the preparation method; a composition for treatment or prevention of hyperuricacidemia, gout, nephritis, chronic renal insufficiency, nephrolith, uremia, urolithiasis, or a uric acid-related disease, the composition containing the compound of chemical formula I at a dose of more than 2 mg and equal to or less than 10 mg and being orally administered once a day; and a hydrochloride 1.5 hydrate of the novel compound of chemical formula I.

Abstract: Provided are novel crystalline forms of a spiro-compound which acts as a muscarinic acetylcholine receptor agonist. In particular, isolated crystalline polymorphs of (S)-2-ethyl-8-methyl-1-thia-4,8-diazaspiro[4.5]decane-3-one are described which have favorable properties in pharmaceutical manufacture. Also provided are methods to prepare said crystalline polymorphs, and to convert them into each other as well as methods for preparing medicaments containing the same which are suitable for use in the treatment of diseases and disorders that respond to modulation of the muscarinic acetylcholine receptor.

Abstract: Compounds of Formula (I): pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed.

Abstract: This application relates to solid forms and salt forms of the PD-1/PD-L1 inhibitor 4,4?-(((((2,2?-dichloro-[1,1?-biphenyl]-3,3?-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid), including processes of preparation thereof, where the solid forms and salt forms are useful in the treatment of various diseases including infectious diseases and cancer.

Abstract: A biphenyl compound represented by formula (I), a preparation method therefor and an application thereof. The present invention also relates to a pharmaceutical composition that comprises the compound as an active ingredient. The compound is a novel small molecule immunomodulator having excellent oral absorption features and can be used for treating and/or preventing various immunity-related diseases.

Abstract: Described are precursor compounds and methods for atomic layer deposition of films containing scandium(III) oxide or scandium(III) sulfide. Such films may be utilized as dielectric layers in semiconductor manufacturing processes, particular for depositing dielectric films and the use of such films in various electronic devices.

Abstract: The present invention concerns a silane of formula (1) R1aSIR4-a??(1) where the group R1 or each of the groups R1 independently is bound to the silicon via an oxygen atom, comprises a straight or branched hydrocarbonaceous chain having one or more elements, wherein (a) each of the elements has not more than 8 consecutive carbon atoms, each of plural elements of the hydrocarbonaceous chain being separated from the next element by a cleavable group and/or (b) the elements have one or more cleavable groups and any hydrocarbonaceous chains remaining upon cleavage of said group(s) are water soluble, wherein said cleavable groups are selected from ester, anhydride, amide, carbonate, carbamate, ketal, acetal, disulfide, imine, hydrazone and oxime groups, has at least one thiol or a primary or secondary amino group, the group R or each of the groups R is independently a hydrolytically condensable group, and a is 1,2,3 or 4.

Abstract: A gold(III) complex, a conjugate of the gold(iII) complex, a pharmaceutical composition comprising the gold(III) complex and uses and a process for preparing the gold(III) complex. The complex comprises a group of (S{circumflex over (?)}C)-cyclometallated gold(III) complexes containing a 1,1-dithio ligand, which exhibit antibacterial activity against multiresistant microorganisms or against biofilm activity or biofilm disruption. The gold(III) complex has efficacy against a variety of microorganisms and low toxicity.

Abstract: This invention provides improvements to processes for making granular lignin from black liquor. One of the improvements is that the use of a pre-carbonation column reduces the CO2 flow into the sparger of a carbonation column. The pre-carbonation column is used to reduce the pH of the black liquor to about 12. Another improvement is that it has been found that coalescing droplets into a bulk liquid-lignin phase can be enhanced by placing the exit of the carbonation column at or slightly beneath carbonated black liquor/liquid-lignin interface. It has also been found that operating the carbonation settler at a low pressure and pumping the liquid-lignin from the carbonation settler to the acidification reactor operating at a higher pressure allows recycling the vent gas from the acidification reactor to the pre-carbonation column. The invention also provides for a vent gas absorber.

Abstract: It is an object of the present invention to provide a clearing agent, by which after a fusion of the streptavidin mutant and a molecular probe has been administered, the fusion, which is not localized in a target site such as an affected site but remains in the body, can be promptly removed (cleared) from the body. The present invention provides a compound represented by the following formula (1) or a salt thereof: wherein X1a, X1b, X2a and X2b each independently represent O or NH; Y1 and Y2 each independently represent C or S; Z1 and Z2 each independently represent O, S or NH; V1 and V2 each independently represent S or S+—O?; n1 and n2 each independently represent an integer of 0 or 1; L10 and L12 each independently represent a divalent linking group; L11 represents a trivalent linking group; L14 represents a divalent linking group; and Sugar represents a sugar residue.

Abstract: The invention discloses a panaxadiol glycoside derivative and a preparation method and application thereof. Such compounds show strong anti-inflammatory effects in vitro and in animal model experiments, and thus can be used to prepare anti-inflammatory drugs, especially can be used for treating asthma and COPD. In the experiment, the above-mentioned compounds have obvious effects on asthma and COPD, and the efficacy of the high-dose group is superior than that of dexamethasone and budesonide. Even under the dose much exceeding the therapeutic dose, no obvious affect on blood routine and blood glucoseis observed. It has high industrial prospects in the field of anti-inflammatory drugs, especially in the field for treating asthma and COPD.

Abstract: The present invention relates to a cocrystal of progesterone, which is formed by the active ingredient progesterone and a cocrystal former which is selected from isophthalic acid, 4-formylbenzeneboronic acid and 3-nitrophthalic acid. The present invention also relates to the method for preparing the cocrystal of progesterone and use thereof for increasing the thickness of endometrium, improving progesterone's solubility or increasing progesterone's permeation rate.

Abstract: Provided herein are anti-infective peptides and uses thereof. Such anti-infective peptides are useful against bacteria and viruses. Also provided herein are compositions comprising said anti-infective peptides.

Abstract: Fusion peptide inhibitors of human coronavirus 229E are provided. The fusion peptide inhibitors of HCoV-229E include peptide #121 (SEQ ID NO: 2: HVLGDISGINASVVQIQKEIDRLNEVAKNLHESLIYLQE), and peptide #125 (SEQ ID NO: 3: HRLRQIRGIRARVVQIQKEIWRLNEVAKLLNESLIYLQE). The fusion peptide inhibitors of HCoV-229E may be administered to a subject in need thereof to inhibit or prevent HCoV-229E cellular entry or infection with HCoV-229E. The fusion peptide inhibitors of HCoV-229E may also be used in HCoV-229E inhibition assays.

Abstract: Disclosed are adeno-associated viral vectors and plasmids encoding the same. Also disclosed are methods of using adeno-associated viral vectors to deliver a protein of interest to the subject. The disclosed vectors have phenotypes including but not limited to increased retention in the blood of a subject, avoidance of the liver, and transduction of the brain and other tissues.

Abstract: The invention relates to composite antigens comprising a peptide with contiguous amino acid sequence derived from a plurality of antigenic epitopes of one or more pathogens that induces an immune response in a mammal that is protective against infection by the one or more pathogens. In addition. The invention also relates to antibodies to composite antigens of the invention and to methods of administering vaccines comprising antigens or vaccines of antibodies for treating and/or preventing an infection.

Abstract: The present disclosure relates to relates methods and associated compositions that provide fast, efficient site-selective conjugation of a protein, such as the pore-forming protein ?-hemolysin, to a biomolecule, such as a DNA polymerase, and the use of such site-selective protein-biomolecule conjugates in nanopore devices and methods.

Abstract: Provided herein are oligomeric reagents, including oligomeric reagents of streptavidin or a streptavidin mutein, compositions thereof, and methods for manufacturing oligomeric reagents, including methods for reliably manufacturing oligomeric particle reagents of a desired size. In some cases, the reagents are oligomeric particle reagents containing a plurality of binding sites for agents, and thus the one or more agents are multimerized by reversibly binding to the oligomeric particle reagent, e.g., thereby creating a multimerized oligomeric particle reagent, having stimulatory agents multimerized thereon. Also provided are methods for using the oligomeric reagents for incubation or culturing, such as to induce stimulation of expansion, activation, and/or survival, of a composition of cells such as a population of lymphocytes.

Abstract: Peptide-immuno-oncology agent complexes (“peptide-I/O complexes”) that can home, target, migrate to, are directed to, are retained by, accumulate in, penetrate, or bind to the tumor microenvironment, tumor tissues, or cells or compartments or cytosol of cells thereof, or any combination thereof, are disclosed. Additionally disclosed are peptide-I/O complexes that can cross the blood-brain barrier. Pharmaceutical compositions and uses for peptide-I/O complexes comprising such peptides are also disclosed. Such compositions can be formulated for targeted delivery of an immuno-oncology agent (“I/O”) to the tumor microenvironment. Targeted compositions of the disclosure can deliver peptide-I/O complexes to target regions, tissues, structures or cells targeted by the peptide.

Abstract: The present invention concerns a structurally distinct immunosuppressive mimic of TGF-? that is a potent inducer of murine and human regulatory T cells and provides a therapeutic agent for the treatment of inflammatory disorders. Disclosed herein is a novel parasite TGF-? mimic which fully replicates the biological and functional properties of TGF-?, including binding to mammalian TGF-? receptors and inducing Foxp3+ Treg in both murine and human CD4+ T cells. This TGF-? mimic shares no homology to mammalian TGF-? or other members of the TGF-? family, but s distinctly related to the component control protein (CCP) superfamily.

Abstract: The present disclosure provides a polypeptide and method for treating and/or preventing nephrotic syndrome, such as but not limited to those associated with minimal change disease and membranous nephropathy, and conditions related to nephrotic syndrome, such as but not limited to, proteinuria and edema, as well as diabetic nephropathy, diabetes mellitus, lupus nephritis or primary glomerular disease. The present disclosure further provides methods for reducing proteinuria and other disease states as discussed herein. Such methods comprise the therapeutic delivery of an Angptl4 polypeptide or Angptl4 polypeptide derivative to a subject.

Abstract: The present disclosure relates to compositions and methods for modulating gene expression and in particular to DNA binding proteins and their use for increasing expression of Klotho. In some examples, the present disclosure provides an isolated or recombinant DNA binding protein comprising or attached to a transcriptional activation domain wherein the DNA binding protein binds to a target sequence within or near a Klotho gene.

Abstract: Disclosed is a polypeptide having a phase transition behavior, wherein the polypeptide consists of a Val-Pro-Gly-Xaa-Gly pentapeptide repeat or a Val-Pro-Ala-Xaa-Gly) pentapeptide repeat, and the polypeptide includes a [Val-Pro-Gly-Xaa-Gly]n or a [Val-Pro-Ala-Xaa-Gly]n (SEQ ID NO:2) pentapeptide repeat. In addition, the present invention provides a multi-stimuli polypeptide composed of polypeptide-calmodulin-polypeptide having a phase transition behavior and a hydrogel prepared using the same. A dynamic protein hydrogel according to the present invention may be used as a drug carrier, as a scaffold for tissue engineering or as a kit for tissue or organ regeneration.

Abstract: The present invention relates to the provision of a recombinant AIM that maintains functions, does not multimerize, and is not inactivated by IgM (e.g., a protein containing an amino acid sequence wherein cysteine at amino acid number 168 of the amino acid sequence shown in SEQ ID NO: 1 is substituted with another amino acid, and the like).