Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: or a pharmaceutically acceptable salt, wherein the variables are as devined herein. Moreover, The compounds of this invention have formula I-A: or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

Abstract: Provided are 6-5 membered fused pyridine ring compounds according to Formula (I) or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising these compounds and their use in therapy. In particular, provided is the use of 6-5 membered fused pyridine ring compounds in the treatment of Bruton's Tyrosine Kinase (Btk) mediated disorders.

Abstract: Provided are crystalline forms of N-[4-[2-(2-amino-4, 7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]ben-zoyl]-L-glutamic acid, pemetrexed diacid, and processes for the preparation thereof.

Abstract: Crystals of a dispiropyrrolidine compound or a salt thereof which inhibits the action of Mdm2 are provided. The present invention provides crystals of (3?R,4?S,5?R)-N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6?-chloro-4?-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2?-oxo-1?,2?-dihydrodispiro[cyclohexane-1,2?-pyrrolidine-3?,3?-indole]-5?-carboxamide or a salt thereof which inhibits Mdm2 and has anti-tumor activity. The present invention also provides a medicament comprising the same.

Abstract: Crystals of a dispiropyrrolidine compound or a salt thereof which inhibits the action of Mdm2 are provided. The present invention provides crystals of (3?R,4?S,5?R)—N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6?-chloro-4?-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2?-oxo-1?,2?-dihydrodispiro[cyclohexane-1,2?-pyrrolidine-3?,3?-indole]-5?-carboxamide or a salt thereof which inhibits Mdm2 and has anti-tumor activity. The present invention also provides a medicament comprising the same.

Abstract: The present invention provides hexahydrofuropyrroles as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.

Abstract: A crystalline form of tritoqualine hydrochloride and also a process for obtaining same. The process for obtaining tritoqualine hydrochloride is made of dissolving tritoqualine base in an alcohol, in particular a lower aliphatic alcohol, such as ethanol, in the presence of hydrochloric acid until a solution in the supersaturated state is obtained. Through successive additions of ether, in particular of ethyl ether, the tritoqualine hydrochloride will subsequently be able to crystallize. The product can be applied to the preparation of pharmaceutical formulations.

Abstract: This invention relates to processes and intermediates for making {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, useful in the treatment of diseases related to the activity of Janus kinases (JAK) including inflammatory disorders, autoimmune disorders, cancer, and other diseases.

Abstract: The present invention is related to novel 20-sulfonylamidine derivatives of camptothecin (1), method of synthesizing the same, and use thereof as an antitumor agent, for examples an antitumor agent for treating nasopharyngeal, lung, breast or prostate cancer.

Abstract: An artificial antigen of aflatoxin biosynthetic precursor Sterigmatocystin (ST) and a method for preparing same. Firstly, hydroxyacetic acid is reacted with the double bound of the difuran ring in the aflatoxin biosynthetic precursor ST, yielding an aflatoxin biosynthetic precursor ST hapten with an active carboxymethoxy group. Secondly, a carboxyl group on the ST hapten is attached to an amino group on a carrier protein. At last, the artificial antigen of aflatoxin biosynthetic precursor ST is obtained by dialysis and lyophilize.

Abstract: The present invention belongs to the field of medicinal technique, specifically relates to nitrogen-containing heterocyclic ring-substituted dihydroartemisinin derivatives and their optical isomers according to formula I or II; wherein substituent X, Y, R, R1, R2, R3 and R4 are as defined in the Description. The derivatives and compositions thereof can be prepared into clinically acceptable tablets, capsules, injections, ointments, etc., and thus have pharmaceutical uses in the treatment and/or prevention of cancers.

Abstract: The present invention relates to compounds that inhibit activity of the histone lysine methyltransferase, Enhancer of Zeste Homolog 2 (EZH2), pharmaceutical compositions comprising the compounds, and methods of using the compounds to treat cancer, such as hematologic and solid tumors.

Abstract: The invention relates to a TRPM8 modulator for achieving a cooling effect on the skin or a mucous membrane.

Abstract: Provided are condensed 5-oxazolidinone derivatives and pharmaceutically permissible salts thereof, which have excellent anticoagulant effects, are well absorbed orally, and are useful as therapeutic drugs for thrombosis, etc. Compounds represented by formula (1) and pharmaceutically permissible salts thereof. [In the formula, L represents a C1-C4 alkylene group that may be substituted; R11 and R12 each independently represent a hydrogen atom or C1-C6 alkyl group, etc. that may be substituted; X1 represents N or CR1; R1 and R2 each independently represent a hydrogen atom, halogen atom, or C1-C6 alkyl group; Ra represents a C4-C7 cycloalkyl group, etc. that may be substituted; and Rb represents a hydrogen atom, etc.

Abstract: The present invention provides substituted bicyclic pyrazolone compounds, which are used to inhibit or modulate the activity of receptor tyrosine kinases, especially Axl, Mer, c-Met and Ron. The invention also provides pharmaceutical compositions comprising the compound disclosed herein, and a method of preventing, treating or lessening the severity of a proliferative disorder in a patient with the compounds or the pharmaceutical compositions disclosed herein.

Abstract: A non-hydroxylic-solvent soluble silver complex has a reducible silver ion complexed with an ?-oxy carboxylate and a primary alkylamine. This non-hydroxylic-solvent soluble silver complex can be represented by the following formula (I): (Ag+)a(L)b(P)c?? (I) wherein L represents the ?-oxy carboxylate; P represents the primary alkylamine; a is 1 or 2; b is 1 or 2; and c is 1, 2, 3, or 4, provided that when a is 1, b is 1, and when a is 2, b is 2. Such complexes can be incorporated into photosensitive compositions that are then used to provide photosensitive thin films or photosensitive thin film patterns. The reducible silver ions can be quickly and efficiently reduced to electrically-conductive silver metal upon exposure to UV-visible radiation in various methods.

Abstract: The disclosure provides an improved synthesis for a zinc-lysine complex having the formula [Zn(C6H14N2O2)2Cl]+Cl?, in which a zinc compound selected from ZnO and ZnCl2, is reacted with a lysine compound selected from lysine and lysine.HCl, in aqueous acid. The disclosure also provides oral care and personal care compositions comprising the complex prepared by the synthesis, and methods of using these complexes and compositions.

Abstract: Described is a method for producing alkenyl halosilanes by reacting alkenyl halide selected from the group comprising vinyl halide, vinylidene halide, and allyl halide with halosilane selected from the group comprising monohalosilane, dihalosilane, and trihalosilane in the gas phase in a reactor comprising a reaction tube (1) that has an inlet (2) at one end and an outlet (3) at the other end, said reactor further comprising an annular-gap nozzle (4) that is mounted on the inlet (2), extends into the reaction tube (1), and has a central supply duct (5) for one reactant (7) and a supply duct (6), which surrounds the central supply duct (5), for the other reactant (8). In order to carry out said method, alkenyl halide is injected into the reaction tube (1) through the central supply duct (5), halosilane is injected thereinto through the surrounding supply duct (6), and both substances flow through the reaction tube (1) in the direction of the outlet (3).

Abstract: The disclosure generally relates to a process for the preparation of compounds of formula I, including synthetic intermediates which are useful in the process.

Abstract: The present invention is directed to crystalline polymorphs of benfotiamine, its methods of preparation and its use thereof. Five crystalline polymorphs of benfotiamine are designated as crystalline forms A, B, C, D and E, and may be distinguished by their respective patterns of X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), infrared spectroscopy (IR), raman spectroscopy, moreover by their diverse preparing process. The crystalline polymorphs of the present invention are useful as they act in treating Vitamin B1 deficiency, metabolic disorders, mental illness and disorders, diabetes complications, neurodegerative diseases. Further the present invention is a process for preparing and transforming diverse crystalline form of benfotiamine through different synthesis routes and varied solvents and combinations. The crystalline polymorphs of the present invention are basically pure.

Abstract: Heterocyclic compounds of formula (I), methods for their preparation, pharmaceutical compositions containing such a compound and their therapeutic uses.

Abstract: A compound of Formula (I) wherein Y1, Y2, X1, X2, R1, R2, R3, R4, R5, R6, R8, and R9 are as defined herein; and pharmaceutically acceptable salts and tautomers thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, in the treatment of diseases in which modulation of STING (Stimulator of Interferon Genes) is beneficial, for example inflammation, allergic and autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes and as vaccine adjuvants.

Abstract: Sulfur chelated ruthenium compounds represented by the following formula: wherein M indicates the ruthenium metal bound to a benzylidene carbon; R represents C1-C7 alkyl group or optionally substituted aryl; X1 and X2 each independently represent halogen; Y1 and Y2 each independently denote unsubstituted or alkyl-substituted phenyl; and Z independently represents hydrogen, electron withdrawing or electron donating substituent, with m being an integer from 1 to 4, and processes and compositions related thereto.

Abstract: The present invention relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, intermediates thereto, and uses thereof. QS-7 is a potent immuno-adjuvant that is significantly less toxic than QS-21, a related saponin that is currently the favored adjuvant in anticancer and antiviral vaccines. Tedious isolation and purification protocols have hindered the clinical development of QS-7. A novel semi-synthetic method is provided wherein a hydrolyzed prosapogenin mixture is used to synthesize QS-7, QS-21, and related analogs, greatly facilitating access to QS-7 and QS-21 analogs for preclinical and clinical evaluation.

Abstract: The present invention provides nucleoside phosphoramidate compounds of Formula I, where R1, R2a, R2b, R4, R5a, R5b, Rb5, Rb6 and D are as defined herein. The invention further includes pharmaceutical compositions comprising a compound of Formula I, methods of use of these compounds for treating a viral infection, and methods of producing these compounds.

Abstract: This invention provides methods for attaching a nucleic acid to a solid surface and for sequencing nucleic acid by detecting the identity of each nucleotide analog after the nucleotide analog is incorporated into a growing strand of DNA in a polymerase reaction. The invention also provides nucleotide analogs which comprise unique labels attached to the nucleotide analog through a cleavable linker, and a cleavable chemical group to cap the —OH group at the 3?-position of the deoxyribose.

Abstract: The present invention provides novel anhydrous polymorph forms of [(2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)]methyl nitrate (compound A), a selective adenosine A1 receptor agonist with a number of therapeutic uses including the treatment of elevated intra-ocular pressure. Also provided are methods for the preparation of the anhydrous polymorphic forms of compound A, pharmaceutical compositions and methods of treatment.

Abstract: The invention provides compounds of formula (I) with substituents as specified in claim 1 for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceuticals compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to over-expression of O-GlcNAcase or accumulation of O-GlcNac.

Abstract: The present invention is directed to n-alkylated synthetic nucleosides of high regiospecific purity and oligonucleotides that can be utilized for studies on reversal of cytotoxic and mutagenic DNA damage, and as diagnostic tools.

Abstract: The present invention relates to a method for preparing a concentrate of polyvalent immunoglobulins with view to therapeutic use, from an initial solution of blood plasma or a plasma fraction enriched with immunoglobulins, comprising the steps for removing the protein contaminants by precipitation with caprylic acid in order to obtain a solution free of proteases, and for separating by chromatography on a fluidized bed the solution free of proteases, said method allowing a concentrate of human polyvalent immunoglobulins with a yield of more than 4.5 g of immunoglobulins per liter of blood plasma applied to be obtained.

Abstract: This invention relates to a method of inhibiting neuronal cell death, including protecting neuronal cells from cell death and the effects of stress, such as high or low pH, comprising administering to the cells an effective amount of Teneurin C-terminal Associated Peptide (TCAP). The invention provides the use of TCAP to prevent and/or treat a number of brain conditions, such as hypoxia-ischemia and brain alkalosis or various brain or spinal cord injuries due to physical or physiological stresses. In one aspect the invention provides a use of TCAP to increase ?-tubulin, ?-actin levels in neuronal cells and/or to increase fasciculation among neuronal cells, in culture or in tissue. In another aspect, the invention provides a method of treating various pH induced neuronal conditions.

Abstract: The methods and compositions described herein relate, in part, to the generation of a synthetic degradation system in E. coli that provides tunable control of the protein level of targeted genes by using components of the Mesoplasma florum tmRNA system. Provided herein are degradation tag variants that permit independent control of both the initial level and inducible degradation rate of attached proteins.

Abstract: Novel peptide inhibitors of GSK-3, compositions containing same and uses thereof are disclosed. The novel peptide inhibitors are converted to inhibitors of GSK-3 upon interacting with the enzyme's catalytic site and hence act as disease-selective inhibitors for treating conditions associated with increased activity and/or expression of GSK-3. Each of the disclosed peptides is independently of no more than 15 amino acid residues, and has an amino acid sequence which comprises a ZX1X2X3Z(p) recognition motif of GSK-3, wherein Z(p) is a phosphorylated serine or threonine residue; Z is a phosphorylatable serine or threonine residue, and each of X1, X2 and X3 is independently any amino acid, as defined in the specification. Further disclosed are methods of identifying a putative substrate-competitive peptide inhibitor of GSK-3 which are effected by computational modeling and screening.

Abstract: The present invention relates to a complex of a protein comprising zinc oxide-binding peptides and zinc oxide nanoparticles, to the use thereof as a drug delivery carrier for manufacturing medicines, and to a vaccine composition and a contrast agent comprising the composite. The protein comprising zinc oxide-binding peptides significantly improves the in vivo availability of zinc oxide-binding peptides, and therefore the complex of the present invention can be used not only as a drug delivery carrier for in vivo drug delivery or intracellular drug delivery, but also for in vivo imaging or cell imaging. The complex can be used for producing separating agents for effectively separating biological materials, therapeutic agents for hyperthermia, etc., contrast agents for MRI, and beads applicable to biosensors.

Abstract: The present invention relates to highly potent ligands at the ghrelin receptor to influence food intake or other conditions.

Abstract: The present invention provides polypeptides and compositions thereof for treating or limiting respiratory syncytial virus infection, and computational methods for designing such polypeptides.

Abstract: The present invention relates to novel adenovirus strains with an improved seroprevalence. In one aspect, the present invention relates to isolated polypeptides of adenoviral capsid proteins such as hexon, penton and fiber protein and fragments thereof and polynucleotides encoding the same. Also provided is a vector comprising the isolated polynucleotide according to the invention and adenoviruses comprising the isolated polynucleotides or polypeptides according to the invention and a pharmaceutical composition comprising said vector, adenovirus, polypeptide and/or polynucleotide. The invention also relates to the use of the isolated polynucleotides, the isolated polypeptides, the vector, the adenoviruses and/or the pharmaceutical composition for the therapy or prophylaxis of a disease.

Abstract: The present invention pertains to fields of biochemistry and molecular biology, relates to an ?O-superfamily conotoxin peptide, pharmaceutical composition thereof, preparation method and use thereof. The present invention further relates to a propeptide of the conotoxin peptide, nucleic acid construct thereof, expression vector and transformed cell thereof, and fusion protein thereof. The present invention further relates to a method for blocking acetylcholine receptors as well as a use of the conotoxin peptide in the manufacture of a medicament. The new ?O-superfamily conotoxin peptide of the present invention is capable of specifically blocking acetylcholine receptor (nAChRs) (e.g., ?9?10 nAChR), and NMDA receptor (e.g.

Abstract: The present invention relates to C-terminal modified Protoxin II peptides that selectively inhibit the Nav1.7 sodium channel; the present invention also relates to pharmaceutical compositions useful for prophylactic or therapeutic treatment of a disorder responsive to the blockade of sodium ion channels, especially Nav1.7 sodium ion channels; the present invention further provides methods of treating a disorder responsive to the blockade of sodium channels, and particularly Nav1.7 sodium channels, in a mammal suffering from excess activity of said channels.

Abstract: The invention relates to a peptidomimetic of an NPC-1 epitope on the MUC5AC protein which is differentially expressed in pancreatic and colorectal cancer, and diagnostic and therapeutic usages. Further, antibodies that selectively bind the NPC-1 epitope peptidomimetics and may be used in diagnostic and therapeutic methods.

Abstract: The present invention is directed to GDF-5 related proteins having an improved capability of inducing cartilage formation and a reduced capability of inducing bone formation. The novel proteins are particularly useful in the treatment of cartilage defects, wherein the formation of bone tissue is undesirable.

Abstract: Described herein is insulin, an insulin-like growth factor, parathyroid hormone, a fragment of parathyroid hormone, or a parathyroid hormone related protein that includes at least one bone targeting moiety, wherein the bone targeting moiety is covalently bonded to the peptide. Also described herein are the methods of making these compositions that prevent or treat conditions associated with bone loss and preventing bone fractures, and/or the inability to initiate de novo bone turnover and stimulate bone fracture repair.

Abstract: The present application relates to novel peptide-based compounds, optionally comprising an immunoactive built-in adjuvant, compositions comprising these compounds and their use, in particular for the treatment of diseases, disorders or conditions characterized by or associated with ?-amyloid accumulation. In particular, the present application includes compounds of Formula I, and compositions and uses thereof: [Ra-NP]m-Lp (I).

Abstract: The disclosure provides OX40L huIgG4 fusion polypeptide subunits comprising a human IgG4 Fc domain, a trimerization domain, and the receptor binding domain of Ox40 ligand, where the fusion polypeptide subunits can self-assemble into hexameric proteins. Also provided are methods of making fusion polypeptide subunits and hexameric proteins, and methods of use, e.g., treatment of cancer.

Abstract: Methods of generating sequence diversity in a protein, such as a ligand-binding protein, are provided. The methods comprise targeted introduction of two or more recombination signal sequences (RSSs) into the protein coding sequence and introduction of the modified protein coding sequence into a recombination-competent host cell, specifically a recombination-competent host cell that is capable of expressing at least RAG-1 and RAG-2, thereby allowing for recombination of the protein coding sequence and expression of variant proteins. Also provided are polynucleotides comprising a nucleic acid sequence encoding a target protein, such as a ligand-binding protein, and comprising two or more RSSs, and compositions and host cells comprising same.

Abstract: The present invention provides monoclonal antibodies that bind to the Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) spike protein, and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that bind to MERS-CoV spike protein. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing MERS-CoV activity, thus providing a means of treating or preventing MERS infection in humans. In some embodiments, the invention provides for a combination of one or more antibodies that bind to the MERS-CoV spike protein for use in treating MERS infection. In certain embodiments, the one or more antibodies bind to distinct non-competing epitopes comprised in the receptor binding domain of the MERS-CoV spike protein.

Abstract: The invention features a novel influenza antibody that specifically binds to influenza hemagglutinin and reduces or inhibits hemagglutinin binding to sialic acid. The invention also provides methods, compositions, and kits featuring the novel antibody and its use in preventing or treating influenza infection.

Abstract: The invention relates to isolated, synthetic or recombinant antibodies and functional parts thereof specific for multiple influenza A virus subtypes. The invention further relates to the use of such antibodies for diagnosis of an influenza A virus infection and as a medicament and/or prophylactic agent for at least in part treating or alleviating symptoms of an influenza A virus infection.

Abstract: The present invention provides methods for treatment or prophylaxis of viruses, particularly influenza virus, by administration of agents, particularly neutralizing antibodies or active fragments thereof, directly to the respiratory tract, including by intranasal or inhalation administration. The invention provides compositions suitable for intranasal or inhalation treatment and administration. The invention includes methods for treatment or prophylaxis combining intranasal or inhalation administration with intraperitoneal or intravenous administration of antibodies.

Abstract: The disclosure relates to human isolated, synthetic or recombinant antibodies or functional parts thereof, specific for the RSV G protein. Antibodies specific for the RSV G protein are particularly suitable for counteracting RSV and symptoms, such as inflammation, resulting from an RSV infection. The disclosure further relates to the use of such RSV G-specific antibodies for diagnosis of an RSV infection and as a medicament and/or prophylactic agent for, at least in part, treating or alleviating symptoms of a Respiratory Syncytial Virus infection and/or a Respiratory Syncytial Virus related disorder.