Abstract: Plakortinic acids A (2) and B (3), two polyketide endoperoxides having an unprecedented bicyclo[4.2.0]octene unit, were isolated as minor constituents from the sponge-sponge symbiotic association Plakortis halichondrioides-Xestospongia deweerdtae from Puerto Rico, along with the known epiplakinic acid F (1). The molecular structures of 2 and 3 were determined mainly on the basis of NMR spectroscopy. Due to the structural similarities, 2 and 3 are thought to be biosynthetically related to 1. Biological screening for cytotoxic activity against two human tumor cell lines revealed that these novel metabolites are very active at low to sub-micro molar concentration.

Abstract: Disclosed are compounds, for example, a compound of formula I, wherein R, R0, R1-R8, n, X, Y, Y?, and E are as described herein, pharmaceutical compositions containing such compounds, and methods of treating or preventing a disease or condition for example, cancer, mediated by the ras gene.

Abstract: BA-1049 (R) and its active metabolite are disclosed. Also disclosed are pharmaceutical formulations containing BA-1049 (R) or its active metabolite.

Abstract: The present invention provides compounds useful as inhibitors of PAD4, compositions thereof, and methods of treating PAD4-related disorders.

Abstract: The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses, in particular in the treatment of diseases or disorders associated to increased relative to physiological or desired RhoJ/Cdc42 levels of expression or function.

Abstract: A method for preparing a tyrosine kinase inhibitor and a derivative thereof are described. In particular, the present method has a short synthesis route, low costs, easy operation, and is suitable for large-scale production.

Abstract: The present invention provides intermediates useful for the synthesis of an aminopyrimidine derivative or pharmaceutically acceptable salt thereof having a selective inhibitory activity against protein kinases, especially against the protein kinases for mutant epidermal growth factor receptors; and processes for preparing the same. And also, the present invention provides novel intermediates useful for said process and processes for preparing the same.

Abstract: The invention relates to substituted ureas, and compositions comprising the same, which in certain embodiments are useful for treating and/or preventing pain in a subject in need thereof.

Abstract: A crystal form of a compound 1 and a method for preparing the same, further comprising an application of the crystal form in the preparation of a drug for treating diseases associated with fibrosis.

Abstract: The present disclosure relates to compounds of formula I that are useful as modulators of 7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation (I).

Abstract: The invention encompasses compounds having formula I-V and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK3, may be therapeutically useful.

Abstract: Provided is a novel process for producing a (2S)-2-[(1H-pyrazol-1-yl)methyl]-1,3-oxazinane derivative. More specifically, provided is a process for producing a (2S)-2-[(1H-pyrazol-1-yl)methyl]-1,3-oxazinane derivative represented by formula (1): the process comprising reacting 3-aminopropan-1-ol with glyoxylic acid.

Abstract: The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease or condition in which plasma kallikrein activity is implicated); and methods of treating patients with such compounds; wherein R5, R6, R7, A, B, W, X, Y and Z are as defined herein.

Abstract: The present invention provides, in part, compounds of Formula I, or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: (R1)a, (R2)b, (R3)c, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, thereof: which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention relates to small molecule compounds and their use as HDAC inhibitors and their use in the treatment of various diseases, such as cancer. The present invention further relates to methods for improvement of solubility by introducing basic substituents which offer the opportunity to create pharmaceutically acceptable salts. Moreover, it comprises methods of synthesizing the compounds and methods of treatment.

Abstract: The present invention provides the compound represented by the following formula (I): wherein a moiety represented by formula: or the like. The symbols are defined in the specification. The compounds of the present invention have MGAT2 inhibitory activity, and are useful as a medicine for treatment of MGAT2-associated diseases including obesity, metabolic syndrome, hyperlipidemia, hypertriglyceridemia, hyper-VLDL-triglyceridemia, hyperfattyacidemia, diabetes mellitus, and arteriosclerosis.

Abstract: The present invention relates to compounds of formula I a process for their manufacture, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment of conditions having an association with TRPC5 containing ion channels. R1, R2, R3, R4 and R5 have meanings given in the description.

Abstract: The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis), kits, methods of synthesis, and products-by-process.

Abstract: In the present invention, a composition comprising two types of thienothiophene compounds selected from the group consisting of the compounds indicated by formulas (1) to (4) (in formulas (1) to (4), either one of R1 and R2 represents an alkyl group, an aromatic hydrocarbon group having an alkyl group or a heterocyclic group having an alkyl group, and the other represents a hydrogen atom, an aromatic hydrocarbon group, a heterocyclic group or a substituent represented by formula (5) (in formula (5), R3 represents an aromatic hydrocarbon group or a heterocyclic group)) can form an organic thin film which is homogeneous over a large area, and an organic semiconductor device including the organic thin film is capable of exhibiting high mobility.

Abstract: Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

Abstract: Preparation of O,O-dimethyl phosphoramidothioate and O,O-dimethyl phosphoroamidothioate. A process of making O,O-dimethyl phosphoroamidothioate is described including reacting sulfur with PCl3 to form PSCl3, reacting the PSCl3 formed with methanol to form O-methyl phosphorodichloridothioate, and reacting the O-methyl phosphorodichloridothioate formed with methyl lye to form O,O-dimethyl phosphorochloridothioate in solution in CH2Cl2, and reacting the O,O-dimethyl phosphorochloridothioate formed with sodium hydroxide and ammonium hydroxide to form O,O-dimethyl phosphoroamidothioate in solution in CH2Cl2. Reacting the O,O-dimethyl phosphoroamidothioate formed with catalytic dimethyl sulfate to form methamidophos and reacting the methamidophos formed with acetic anhydride to form N-(methoxy-methylsulfanylphosphoryl) acetamide is also described. Throughout the process, the O,O-dimethyl phosphorochloridothioate and the O,O-dimethyl phosphoroamidothioate formed are maintained in solution in CH2Cl2 at all times.

Abstract: Embodiments of the present disclosure provide for biaryl ligands (also referred to herein as “biaryl compound”), biaryl complexes, methods of making biaryl compounds, methods of making single enantiomers of these biaryl compounds, methods of use (e.g., catalysis), and the like.

Abstract: A method for separating hydrolysis product of biomass is provided. The method includes providing a mixture solution containing a hydrolysis product of biomass and a divalent metal salt, adjusting the pH value of the mixture solution to between 1-4.6, and performing a filtering procedure on the mixture solution using a nanofiltration membrane to obtain a concentrated solution and a filtrate, wherein the concentrated solution mainly includes the hydrolysis product of biomass and the filtrate mainly includes the divalent metal salt.

Abstract: The present invention relates to an industrially feasible and economically viable process for preparation of Bexagliflozin of formula V in significantly high yield and purity.

Abstract: A newly developed butane-tetraol-based amphiphilic compound, a method of preparing the same, and a method of extracting, solubilizing, stabilizing, crystallizing or analyzing a membrane protein using the amphiphilic compound are provided. The butane-tetraol-based compound is found to have a central structure exhibiting chirality, and isomers of the compound have clearly different characteristics according to the stereochemistry of the central structure, thereby making it possible to select compounds suitable for the uses thereof. Also, the compound can be used to effectively extract a membrane protein, which has more various structures and characteristics than conventional compounds, from cell membranes and stably store the membrane protein in an aqueous solution for a long time, and thus analyze the function and structure of the membrane protein.

Abstract: Disclosed are derivatives of amphotericin B (AmB) characterized by improved clinical efficacy with reduced toxicity compared to AmB. Also disclosed are pharmaceutical compositions comprising the AmB derivatives, therapeutic methods of using the AmB derivatives and methods of making the AmB derivatives.

Abstract: A Dengue virus Envelope Dimer Epitope (EDE) wherein the EDE: c) spans the polypeptides of a Dengue virus Envelope polypeptide dimer; and/or d) is presented on a dimer of Envelope proteins; and/or c) is formed from consecutive or non-consecutive residues of the envelope polypeptide dimer, wherein the dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3 and DENV-4.

Abstract: There is provided a method of treating chronic hepatitis B infection (CHB) in a human, comprising the steps of: a) administering to the human a composition comprising a replication-defective chimpanzee adenoviral (ChAd) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc); b) administering to the human a composition comprising a Modified Vaccinia Virus Ankara (MVA) vector comprising a polynucleotide encoding a hepatitis B surface antigen (HBs) and a nucleic acid encoding a hepatitis B virus core antigen (HBc); and c) administering to the human a composition comprising a recombinant hepatitis B surface antigen (HBs), recombinant hepatitis B virus core antigen (HBc) and an adjuvant.

Abstract: The present invention provides compositions comprising randomized in-frame fusion polynucleotides and methods for introducing them into a host organism to obtain desirable phenotypic changes that modulate tolerance to stress, thus creating novel characteristics of the transformed organism.

Abstract: Compositions and methods for controlling pests are provided. The methods involve transforming organisms with a nucleic acid sequence encoding an insecticidal protein. In particular, the nucleic acid sequences are useful for preparing plants and microorganisms that possess insecticidal activity. Thus, transformed bacteria, plants, plant cells, plant tissues and seeds are provided. Compositions are insecticidal nucleic acids and proteins of bacterial species. The sequences find use in the construction of expression vectors for subsequent transformation into organisms of interest including plants, as probes for the isolation of other homologous (or partially homologous) genes. The pesticidal proteins find use in controlling, inhibiting growth or killing Lepidopteran, Coleopteran, Dipteran, Hemipteran, fungi and nematode pest populations and for producing compositions with insecticidal activity.

Abstract: The invention is intended to identify glutathione-S-transferase that exhibits the activities to metabolize and detoxify an isoxazoline derivative, such as pyroxasulfone. The invention provides a method for cultivating a transgenic plant into which a nucleic acid encoding a protein (a or b) below has been introduced in the presence of isoxazoline derivatives: (a) a protein comprising the amino acid sequence as shown in SEQ ID NO: 2; or (b) a protein comprising an amino acid sequence having 80% or higher identity to the amino acid sequence as shown in SEQ ID NO: 2 and having the activity of glutathione-S-transferase.

Abstract: Methods of increasing the biological activity of toxins. Methods of increasing the biological activity of pesticide toxins through the incorporation of pro-regions into nucleic acid constructs for the production of said toxins.

Abstract: The disclosure of the present application relates to a secretory deleted split hand/split foot 1 (sDSS1) protein, the amino acid sequence thereof, the nucleic acid sequence thereof, and the applications of the same. The sDSS1 protein is a secretory protein from higher primate, and can be detected in human serum and cerebral spinal fluid (CSF). The sDSS1 protein can form conjugate with oxidized protein under nonenzymatic condition or with amyloid-beta (A?) polypeptide to reduce formation of A? oligomer. The addition of sDSS1 protein to culture medium can shield the cytotoxicity induced by oxidized protein, A? oligomer, amylin oligomer and glycosylated protein, so as to protect the cells against these toxoproteins. The sDSS1 protein can prolong survival time of senescence-accelerated mice significantly.

Abstract: Among other things, the present disclosure provides technologies for modulating functions of beta-catenin. In some embodiments, the present disclosure provides stapled peptides that interact with beta-catenin. In some embodiments, provided stapled peptides interact with beta-catenin at an Axin-binding site of beta-catenin. In some embodiments, the present disclosure provides compounds, compositions and methods for preventing and/or treating conditions, disorders and diseases that are associated with beta-catenin.

Abstract: A synthetic truncated norrin protein is provided. The synthetic truncated norrin protein is a ?24 residue N-terminus norrin truncate relative to SEQ ID. NO. 1 that retains the cysteine-knot motif and frizzled-4 binding properties and has a mutation in the cysteine-knot motif in at least one position 81-90 of SEQ ID. NO. 1 that interferes with protease cleavage of the resulting protein thereby extending the biological half-life thereof in vivo relative to native norrin.

Abstract: Provided herein are compounds comprising peptides that bind Bfl-1. Also provided are compositions containing these peptides and methods of using such peptides in the treatment of cancer that include administering to a subject one of the peptides.

Abstract: A recombinant protein expressing one or more human growth factors, tumor antigens, and/or receptors or epitopes thereof on or within an immunogenic expression creating a recombinant protein in which one or more epitopes are presented on the surface of the sequence in their natural configuration. The growth factor, tumor antigen, and/or receptor, sequence(s) may be expressed within the encoding sequence at appropriate internal positions or at the termini as single expressions or as two or more tandem repeats.

Abstract: Compositions and methods are provided relating to Type III interferons.

Abstract: A process is described for purifying insulin and insulin analogs that comprises high-pressure liquid chromatography with an acidic cation exchange medium performed in the presence of a water miscible organic modifier and at an elevated temperature followed by reverse phase chromatography performed in the presence of a water miscible organic modifier and at an elevated temperature.

Abstract: The present disclosure relates to compositions of insulin-Fc fusion proteins and their use to treat diabetes.

Abstract: A selective IL-6-trans-signalling inhibitor can be used to treat a variety of IL-6-mediated conditions, including inflammatory diseases and cancer. The inhibitor can safely be administered to humans at a variety of doses. Moreover, the inhibitor lessens deleterious effects associated with other IL-6 inhibitors such as lowering neutrophil counts, platelet counts and levels of C-reactive protein.

Abstract: Disclosed herein, are nanoparticles comprising one or more immune-tolerant elastin-like polypeptide tetramers and one or more immune-tolerant elastin-like fusion molecules. Also, disclosed herein are pharmaceutical compositions including the nanoparticles; methods of administering the nanoparticles to patients for the treatment of cancer; and methods of making the nanoparticles.

Abstract: Disclosed herein are compositions comprising arenavirus monoclonal antibodies, as well as therapeutic, diagnostic, and preventative methods using the novel antibodies. Preventative methods include preparation of vaccines, as well as factors (e.g. small molecules, peptides) that inhibit Old World arenavirus infectivity, including LASV and LCMV. In some embodiments, the antibodies provide pan-arenavirus protection against a number of arenavirus types and strains. Diagnostic and therapeutic antibodies including neutralizing antibodies for the prevention and treatment of infection by LASV and other arenaviruses are also disclosed, as well as new tools and methods for the design, production, and use of arenavirus monoclonal antibodies, including expression in engineered bacterial- and mammalian-based systems.

Abstract: Materials and methods are provided for treatment and/or prevention of Staphylococcal diseases and disorders such as infection and dermal inflammation.

Abstract: Described herein are isolated monovalent antibodies or antibody fragments thereof that bind human properdin. Such antibodies are useful in methods of treatment for diseases mediated by alternative complement pathway dysregulation.

Abstract: The invention relates to the combined use of certain bispecific, VEGF and Ang2 binding molecules with PD1 antagonists for the treatment of cancer. It further relates to pharmaceutical compositions and kits comprising such binding molecules and antagonists.

Abstract: Methods and systems for administering anti-TNF therapy to subjects who have been determined to display a gene expression response signature established to distinguish between responsive and non-responsive prior subjects who have received the anti-TNF therapy.

Abstract: Monoclonal antibody that specifically binds IL-1RAcP, or an antigen binding fragment thereof, comprising: a) a heavy chain variable region (VH) comprising CDR1H, CDR2H and/or CDR3H, wherein the CDR1H region comprises an amino acid sequence selected from the group of SEQ ID NO: 155-231, wherein the CDR2H region comprises an amino acid sequence selected from the group of SEQ ID NO: 232-308, and wherein the CDR3H region comprises an amino acid sequence selected from the group of SEQ ID NO: 309-385; and b) a light chain variable region (VL) comprising CDR1L, CDR2L and/or CDR3L, wherein the CDR1L region comprises an amino acid sequence selected from the group of SEQ ID NO: 386-462, wherein the CDRL2 region comprises an amino acid sequence selected from the group of SEQ ID NO: 463-539, and wherein the CDR3L region comprises an amino acid sequence selected from the group of SEQ ID NO: 540-616 The monoclonal antibody is characterized in that it inhibits IL-1RAcP induced NFkB activity, useful in treatment of IL-1RAcP

Abstract: Disclosed are a chimeric antigen receptor (CAR) targeting CLD18A2, and preparation method and use thereof. The extracellular binding region of the CAR comprises a protein specifically recognizing CLD18A2. The immune effector cell modified by the CAR can be used to treat tumors such as pancreatic cancer and stomach cancer.