Abstract: The present invention provides a salt of (S)-7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one and an acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, malonic acid, maleic acid, tartaric acid, methanesulfonic acid, benzenesulfonic acid and toluenesulfonic acid; or a crystal thereof with a potential to be used as drug substance in pharmaceuticals.

Abstract: The invention relates to a compound of Formula I or IA and methods of treating cystic fibrosis comprising the step of administering a therapeutically effective amount of a compound of Formula I or IA to a patient in need thereof:

Abstract: Mitogen activated protein kinase (MAPK) inhibitors disclosed herein are useful for the treatment of diseases of the respiratory tract, such as chronic eosinophilic pneumonia, asthma, COPD, adult respiratory distress syndrome (ARDS), exacerbation of airways hyper-reactivity consequent to other drug therapy, and airways disease that is associated with pulmonary hypertension.

Abstract: The present invention relates to compound of formula (I) as tricyclic hexahydrodiazepinoquinolines carrying a cyclic substituent, useful for modulating the 5-HT2C receptor and preventing and/or treating conditions and disorders that respond to the modulation of the 5-HT2C receptor. The present invention also relates to methods for producing compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for preventing or treating conditions and disorders that respond to the modulation of the 5-HT2C receptor by administering compounds of formula (1) or pharmaceutical compositions thereof.

Abstract: The present invention relates to new crystalline forms of a purine derivative which exhibits excellent anti-tumor activity. The invention also relates to a pharmaceutical composition containing said crystalline forms as an active ingredient, and use thereof in the prevention or treatment of disease. The invention further relates to a process for preparing the crystalline forms.

Abstract: The present invention provides methods of preparing 4-amino-2-butoxy-8-(3-(pyrrolidin-1-ylmethyl)benzyl)-7,8-dihydropteridin-6(5H)-one and related compounds.

Abstract: The present invention provides heteroaromatic derivatives and pharmaceutical acceptable salts and formulations thereof useful in modulating the protein kinase activity, especially phosphatidylinositol 3-kinases (PI3 kinases) and mTOR, and in modulating inter- and/or intra-cellular signaling activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

Abstract: The present teachings provide a compound represented by structural formula (1-0), or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof.

Abstract: Heterocyclic compounds and salts according to formula (I), which are pyrimidinone derivatives, described herein exhibit human neutrophil elastase inhibitory properties, and useful for treating diseases or conditions in which HNE is implicated.

Abstract: It relates to certain compounds having a polycyclic structure and a hydroxamic acid moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to a process for their preparation, as well as to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases.

Abstract: The present invention relates to aryl pyrazoles, and pharmaceutically acceptable salts thereof. The aryl pyrazoles of the present invention are useful as inhibitors of leukotriene A4 hydrolase (LTA4H) and treating LTA4H related disorders. The present invention also relates to pharmaceutical compositions comprising the aryl pyrazoles of the present invention, methods of using these compounds in the treatment of various diseases and disorders, and processes for preparing these compounds.

Abstract: The present disclosure is directed to certain inhibitors of kinases such as ITK, BLK, BMX, BTK, JAK3, TEC, TXK, HER2 (ERBB2), or HER4 (ERBB4), in particular ITK, pharmaceutical compositions comprising such compounds, and method of treating diseases mediated by such kinases.

Abstract: This invention relates to methods for preparing a sodium-glucose transporter 2 (SGLT2) inhibitor, a cocrytalline SGLT2 and (S)-5-oxopyrrolidine-2-carboxylic acid (L-PGA) complex, and intermediates useful in the preparation of the said SGLT2 inhibitor.

Abstract: The present invention relates to glioblastoma inhibiting compounds, in particular gambogic acid amid and derivatives thereof for the treatment of glioblastoma. Moreover, methods for determining whether a treatment with the compounds of the invention is suitable for a patient are disclosed.

Abstract: The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

Abstract: The present invention relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, and/or reducing the risk of microbial infections in humans and animals.

Abstract: A fused heterocyclic compound represented by formula (1) or an N-oxide thereof has an excellent control effect on pests: wherein A1 represents N or the like, A2 represents NR6 or the like, A3 represents CR12 or the like, R1 represents a C1 to C6 chain hydrocarbon group or the like, R2, R4 and R5 are the same or different and represent a C1 to C3 alkyl group optionally having one or more halogen atoms or the like, R3 represents a C1 to C6 chain hydrocarbon group or the like, R6 represents a C1 to C6 chain hydrocarbon group or the like, any one set of R9 and R10, R10 and R11, and R11 and R12 in R9, R10, R11 and R12, together with the carbon atoms to which they are bound, forms a ring, and n represents 0, 1 or 2.

Abstract: The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to oxygen linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumors and cancers as well as other disorders or conditions related to or associated with kinases.

Abstract: The present invention provides (R)-3-Amino-1-butanol (D)-tartarate (IIb); process for its preparation and its conversion to Dolutegravir. The present invention also provides an improved process for the preparation of Dolutegravir (I) or pharmaceutically acceptable salts wherein compound (XVI) is reacted with an optically active acid addition salt of (R)-3-amino-1-butanol (IIa).

Abstract: The present invention relates to compound of formula I, II, III, or IV, and/or a pharmaceutical acceptable addition salt thereof and/or a stereoisomer thereof and/or a solvate thereof, Formulas (I), (II), (III) and (IV) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R11, and R12 are as defined in the claim 1 or as described in detail in the description of the invention, and to the use of said compounds to treat or prevent proliferative disorders and their use to manufacture a medicine to treat or prevent proliferative disorders, particularly cancer such as leukemia. The present invention also relates to pharmaceutical compositions of said compounds and the use of said pharmaceutical compositions to treat or prevent proliferative disorders. The present invention further relates to the use of said compounds as biologically active ingredients, more specifically as medicaments for the treatment of proliferative disorders and pathologic conditions such as, but not limited to, cancer such as leukemia.

Abstract: Monomeric gold(I) complexes as anticancer agents. The gold(I) complexes are coordinated to mixed ligands: one N-heterocyclic carbene ligand and one monodentate dithiocarbamate-based ligand. Pharmaceutical compositions incorporating the gold(I) complexes, methods of synthesis, methods of treating cancer and methods of inhibiting cancer cell proliferation and inducing cancer cell apoptosis are also provided.

Abstract: The present invention provides a compound of Formula I: wherein X, Y, Z, R1 and R2 are as described herein, and salts thereof and therapeutic uses of these compounds for treatment of disorders associated with RAF kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.

Abstract: The present invention provides a compound of Formula I or hydrate thereof, useful for the treatment of diabetes.

Abstract: The invention is directed to processes for synthesizing bicyclic nucleoside antiviral compounds and for synthesizing the intermediates used in the process. The invention is also directed to novel intermediate compounds useful in the process. The antiviral compounds are useful in the treatment of herpes zoster (i.e., varicella zoster virus, VZV, shingles) and for the prevention of post herpetic neuralgia (PHN) resulting from this viral infection.

Abstract: The invention relates to compositions for use in animal models of neurodegenerative disease and methods therefor. More particularly, the invention relates to the use of neurotoxic sterol glycosides or neurotoxic glycolipids, or combinations thereof, in animal models of neurodegenerative disease. Neurotoxicity-modulating chromenols can also be used in these animal models in combination with the neurotoxic sterol glycosides or neurotoxic glycolipids, or combinations thereof.

Abstract: The invention discloses a method of separating a biomolecule from at least one other component in a liquid, comprising a step of contacting said liquid with a separation matrix comprising a solid support and polymer chains bound to said solid support. The polymer chains comprise units derived from a first monomer of structure CH2?CH-L-X, where L is a covalent bond or an alkyl ether or hydroxysubstituted alkyl ether chain comprising 2-6 carbon atoms, and X is a sulfonate or phosphonate group.

Abstract: Disclosed herein are PACE4 inhibitors, compositions comprising PACE4 inhibitors and their uses thereof for lowering PACE4 activity, reducing cell proliferation, reducing tumor growth, reducing metastasis formation, preventing and/or treating cancer. Also provided are methods for lowering PACE4 activity, reducing the proliferation of a cell, reducing tumor growth and/or treating and preventing cancer. Methods for screening PACE4 inhibitors and cell proliferation inhibitors are further provided.

Abstract: The present invention relates to a melanoma antigen peptide comprising the amino acids sequence selected in the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5 or a function-conservative variant thereof. Moreover the invention also relates to a melanoma antigen peptide according to the invention for use in the prevention or the treatment of melanoma in patient.

Abstract: Methods and compositions for increasing a plant's resistance to an insect pest such as the corn rootworm are provided. Methods are provided for overexpression of Crw2, or variants thereof, in a host plant or plant cell to increase resistance to an insect pest in a plant such as maize. Methods are also provided for identifying variants of Crw2 that when incorporated into a plant via transgenic or traditional breeding means increase resistance to an insect pest in a plant such as maize. Also provided are methods for increasing resistance by overexpressing Crw1 and Crw2.

Abstract: A method for preventing neoplastic transformation by inhibition of cell cycle progression into S phase by preventing the inactivation of Retinoblastoma protein (Rb).

Abstract: The present invention relates to a compound of the formula (I), (II), (III), (IV), (V), or (VI) or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing a viral infection using the same.

Abstract: The invention relates to a modified VP1-capsid protein of parvovirus B19 having a reduced phospholipase A2-like enzyme activity as compared to the wild type VP1-capsid protein of parvovirus B19 having the amino acid sequence of SeqID 1.

Abstract: The present invention is generally directed to fusion proteins containing a targeting sequence that targets the fusion protein to the exosporium of a Bacillus cereus family member. The invention also relates to recombinant Bacillus cereus family members expressing such fusion proteins, formulations containing the recombinant Bacillus cereus family members expressing the fusion proteins. Methods for stimulating plant growth and for protecting plants from pathogens by applying the recombinant Bacillus cereus family members or the formulations to plants or a plant growth medium are also described. The invention also relates to methods for immobilizing spores of a recombinant Bacillus cereus family member expressing a fusion protein on plant roots.

Abstract: There is provided an epsilon toxin epitope polypeptide comprising a sequence of at least 10 contiguous amino acids from SEQ ID NO:3, the sequence comprising a mutation of at least one tyrosine residue compared to the equivalent sequence in SEQ ID NO:3, the polypeptide being capable of binding an antibody which binds to SEQ ID NO:5 and having reduced toxicity compared with the toxicity of SEQ ID NO:5. The polypeptide is useful in a method of vaccinating a subject against developing a disease caused by clostridium perfringens and/or caused by (or associated with the presence of) active epsilon toxin.

Abstract: The present invention provides modified tamabidin 2, which is a modified biotin-binding protein comprising an amino acid sequence represented by SEQ ID NO: 2, an amino acid sequence having one or more amino acid mutations in the amino acid sequence of SEQ ID NO: 2, or an amino acid sequence having an identity of not less than 80% to the amino acid sequence of SEQ ID NO: 2 and having biotin-binding activity, wherein an asparagine residue at position 115 of SEQ ID NO: 2 is replaced with cysteine. The modified biotin-binding protein has remarkable heat resistance.

Abstract: The present disclosure provides IDAC compounds capable of presenting two or more signal 1 moieties to a host immune system and methods of using the IDAC compounds to treat or prevent autoimmune disorders in a subject. The present disclosure provides compounds including a modified I-domain peptide having two or more modified lysine residues and two or more signal 1 moieities conjugated to the modified lysine residues of the I-domain peptide and methods of using an making the compounds.

Abstract: The present invention relates to novel chimeric molecules of ficolin-associated polypeptides, such as fusion polypeptides for the use in the treatment of conditions associated with inflammation, apoptosis, autoimmunity, coagulation, thrombotic or coagulopathic related diseases. The present invention further relates to nucleic acid molecules encoding such fusion polypeptides, vectors and host cells used in the production of the fusion polypeptides.

Abstract: A p16 protein variant; a polynucleotide encoding the p16 protein variant; a method for preparing the p16 protein variant; a pharmaceutical composition comprising the p16 protein variant; a method for preventing and/or treating cancer comprising administering the p16 protein variant to a subject; and use of the p16 protein variant in the prophylaxis and/or therapy of cancer.

Abstract: The present invention provides a peptide-type compound which induces secretion of growth hormone and which has the activity of increasing the intracellular calcium ion concentration, wherein at least one amino acid is replaced by a modified amino acid and/or a non-amino acid compound, or a pharmaceutically acceptable salt thereof.

Abstract: Insulin analogs comprising a non-native glycosylation site sequence are provided having high potency and specificity for the insulin receptor. In one embodiment a peptide sequence of greater than 18 amino acids is used as a linking moiety to link human insulin A and B chains, or analogs or derivatives thereof, to provide high potency single chain insulin analogs. In one embodiment the linking moiety comprises one or more glycosylation sites. Also disclosed are prodrug and conjugate derivatives of the insulin analogs.

Abstract: The invention provides compositions and methods for treating leukemia, for example, acute myeloid leukemia (AML) and B-cell acute lymphoid leukemia (B-ALL). The invention also relates to at least one chimeric antigen receptor (CAR) specific to CD123, vectors comprising the same, and recombinant T cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD123 binding domain. The invention also includes methods of bone marrow ablation for use in treatments necessitating bone marrow reconditioning or transplant.

Abstract: Described are polypeptide dimers comprising two soluble gp130 molecules wherein each of said molecules is fused to an Fc domain of an IgG1 protein and wherein the hinge region of the Fc domain is modified resulting in advantageous properties of the dimer. In a particularly preferred embodiment, the hinge region comprises the amino acid sequence motif Ala234-Glu235-Gly236-Ala237. Moreover, a pharmaceutical composition containing said dimer and various medical uses are described.

Abstract: The present invention relates to a method for producing high affinity antibodies that are antigen-specific. The method involves binding a plurality of antibody-producing B-cells from a mammal to a plurality of cognate antigens; sorting the bound antibody-producing B-cell and cognate antigen; amplifying nucleic acid sequences encoding each antibody, or fragment thereof, from the B-cells; and expressing the each antibody in a protein expression system. Antibodies produced in this manner are useful in diagnostic and therapeutic applications.

Abstract: The present invention relates to human monoclonal antibodies derived from human B cells present in the blood of patients who had recovered from infection with influenza A viruses, wherein the monoclonal antibodies have neutralizing activity against influenza A viruses. The anti-influenza A virus monoclonal antibody of the present invention has binding and neutralizing activities against at least one influenza A virus selected from the group consisting of influenza A virus H1, H2 and H5 subtypes, and thus it is useful for the prevention and treatment of a disease caused by the influenza A virus and is also useful for diagnosis of influenza A virus infection.

Abstract: The present invention relates to amino acid sequences that are capable of binding to serum albumin; to proteins and polypeptides comprising or essentially consisting of such amino acid sequences; to nucleic acids that encode such amino acid sequences, proteins or polypeptides; to compositions, and in particular pharmaceutical compositions, that comprise such amino acid sequences, proteins and polypeptides; and to uses of such amino acid sequences, proteins and polypeptides.

Abstract: The invention provides an antibody targeting a cancer antigenic protein specifically expressed on the surface of cancer cells and use thereof in a therapeutic and/or preventive agent for cancer. Specifically, this invention provides an antibody or a fragment thereof which has immunological reactivity with a partial CAPRIN-1 polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 5 or an amino acid sequence having 80% or higher sequence identity to the amino acid sequence, and a pharmaceutical composition for treatment and/or prevention of cancer, comprising the antibody or fragment thereof as an active ingredient.

Abstract: The present invention relates to the amyloid beta peptide (A?) and more specifically to antibodies binding to A? protofibrils and their use in therapy and/or prophylactic treatment of Alzheimer's disease and other disorders associated with A? protein aggregation. Further the invention may relate to diagnosis of such diseases as well as monitoring of disease progression by use of the antibodies of the invention. Further, the invention may relate to veterinary use of the antibodies of the invention.

Abstract: Provided herein are proteins, antibodies, assays and methods useful for modulating growth factor levels and/or activities. In some embodiments, such growth factors are members of the TGF-? superfamily of proteins.

Abstract: A monoclonal secretory IgA antibody, which binds to and neutralizes a human proinflammatory cytokine or which binds to and blocks a human proinflammatory cytokine receptor. The secretory IgA antibody is useful in treating a variety of inflammatory diseases in humans.

Abstract: The present invention relates to a compound which is an antagonist of IL-1 beta or an inhibitor of IL-1 beta expression for use in the treatment or the prevention of aneurysm. In another embodiment, the invention relates to a pharmaceutical composition for use in the treatment or the prevention of aneurysm comprising an antagonist of IL-1 beta or an inhibitor of IL-1 beta expression.