Abstract: The present invention relates to pyrazolopyridazine derivatives. More particularly, it relates to 4-(biphenyl-3-yl)-1H-pyrazolo[3,4-c]pyridazine derivatives of formula (I), and pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, R4 and R5 are as defined in the description. The pyrazolopyridazine derivatives of the present invention modulate the activity of the GABAA receptor. They may useful in the treatment of a number of conditions, including pain and epilepsy.

Abstract: This invention relates to compounds of formula (I). The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK). The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.

Abstract: The present invention provides 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones and 1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-ones of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.

Abstract: Compounds of formula (I) that are capable of acting as purine receptor antagonists, pharmaceutical compositions including the compounds, and methods of making the compounds, are disclosed. The compounds and compositions can be used in treating or preventing disorders related to purine receptor hyperfunctioning.

Abstract: The present invention provides a compound of Formula II, and salts thereof, and a pharmaceutical composition comprising a compound of Formula II: wherein R is hydrogen or an alkyl group having from one to ten carbon atoms, and wherein R3 is hydrogen, an alkyl group having from one to ten carbon atoms, or a halogen. Preferably the compound of Formula II includes wherein R3 is a halogen, and most preferably wherein the halogen is chlorine. Methods of treating a patient with cancer with these compounds are also provided.

Abstract: The invention of the present application provides a compound represented by Formula (I) or a salt thereof, which exhibits an inhibitory activity against at least one kinase selected from the group consisting of Akt kinase, Rsk kinase, and S6K kinase and/or a cell proliferation inhibiting effect and is useful as a prophylactic and/or therapeutic agent for diseases associated with the above-mentioned kinases, particularly cancer.

Abstract: A crystalline modification of triazolopyrazine derivatives binds to a hepatocyte growth factor (HGF) to activate phosphorylation, thereby significantly inhibiting the activity of c-Met kinase triggering cell proliferation, migration, and formation of new blood vessels. Therefore, the compound of the present application may be effectively used for the treatment or prevention of various hyper proliferative disorders mediated by hyper proliferation activation of cells and excessive angiogenesis.

Abstract: Compounds are provided that antagonize vasopressin receptors, particularly the V1a receptor products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof: wherein Q1, Q2, Q3, R2a, R2b, R3 and X are as defined herein.

Abstract: Provided herein are prodrugs of opioid receptor antagonists such as nalmefene and naltrexone, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of behavioral disorders.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: X-A-Y-L-R??(I) 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 provides a compound of formula I: and pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, R4, R5, L1, L2, m, and n, are as described in the specification. Such compounds are inhibitors of VPS34 and thus useful for treating proliferative, inflammatory, or cardiovascular disorders.

Abstract: Analogs of largazole are described herein. Methods of treating cancer, blood disorders, autoimmune disease, and Alzheimer's Disease using largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.

Abstract: A compound of general formula I, wherein X, R1-R4 take various meanings, for use in the treatment of cancer.

Abstract: The present invention relates to a process for the preparation of 2-pyrazolo[1,5-a]pyrazin-2-ylpyrido[1,2-a]pyrimidin-4-one derivatives useful as pharmaceutically active compounds.

Abstract: Compounds according to Formula I and Formula II are potent inhibitors of Arginase I and II activity: where R1, R2, R3, R4, R5, R6, R7, R8, R9, D, M, X, and Y are defined as set forth in the specification. The invention also provides pharmaceutical compositions of the compounds and methods of their use for treating or preventing a disease or a condition associated with arginase activity.

Abstract: A polycyclic compound is represented by Formula 1, where X1, X2, L, R1 to R8, and a to d are as defined in the specification.

Abstract: A method for preparing a 3-((2S,5S)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)propanol derivative by a simple process with high yields, and an intermediate useful for the method.

Abstract: Provided is a nanocrystal comprising a core comprised in a shell, wherein the core comprises a first material of a perovskite structure comprising a first organic cation not exceeding a molar weight of about 45 g/mol, a first divalent metal and a first counter anion, and, wherein the shell comprises a second material of a perovskite structure comprising a second organic cation having a molar weight between about 74 g/mol and about 187 g/mol, optionally the first organic cation, a second divalent metal and a second counter anion. Provided is further a matrix having the nanocrystal as defined above encapsulated therein.

Abstract: The present disclosure involves a composition enriched in compound 61501b, wherein the compound 61501b has a purity of not less than 90% or more. The composition has a significant advantage in preparing a high-purity compound Sp-1. In addition, the present disclosure also provides a preparation method of the composition enriched in compound 61501b. The method adopts a crystallization technique to perform separation and purification, has a simple and convenient operation and good reproducibility, and therefore the compound 61501b in the prepared composition has high purity and quality. Further, the present disclosure also involves a novel crystal form of compound 61501b.

Abstract: Compounds of the general formula (I): or a pharmaceutically acceptable salt thereof, processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.

Abstract: The present invention provides a method for producing a cyclometalated iridium complex, the method including producing a cyclometalated iridium complex by reacting a cyclometalated iridium complex raw material including an organoiridium material with an aromatic heterocyclic bidentate ligand capable of forming an iridium-carbon bond and an iridium-nitrogen bond, and using as the raw material an organoiridium material represented by the following general formula (1). The present invention allows a cyclometalated iridium complex to be produced with a high yield without by-production of a halogen-crosslinked iridium dimer.

Abstract: The invention is directed to platinum(II) complexes comprising dithiocarbamates and methods for treating cancer using these complexes.

Abstract: Disclosed herein are novel compounds of formula (I) and (II), each of which may serve as a reagent to deliver nitric oxide (NO) and a therapeutic agent to treat NO-associated diseases. Also disclosed are a pharmaceutical composition comprising the compound of formula (I) or (II), a composite material comprising the compound of formula (I) or (II), and the uses thereof.

Abstract: The invention provides a compound of the formula: and a capture support of the formula: wherein R1, R2, R3, R6, A, B, D, E, J, K, Q, W, and Z are as defined herein. The invention also provides a method of purifying an oligonucleotide or an oligonucleotide analog composed of “b” nucleotides from a mixture comprising the oligonucleotide or oligonucleotide analog and at least one oligonucleotide or oligonucleotide analog composed of “a” nucleotides, wherein b?a, comprising use of the compound and the capture support.

Abstract: The present invention provides a mangiferin-6-O-calcium salt and a preparation process thereof. In addition, use of the mangiferin-6-O-calcium salt as defined in claim 1 as an intermediate in the preparation of a mangiferin-6-O-berberine salt is also provided.

Abstract: The invention relates to novel substance mixtures which can be used as aroma compositions to enhance the sweet taste of oral preparations.

Abstract: NNA-derived specific adducts represent an integrated biomarker of exposure to thirdhand smoke (THS) as NNA is unique to THS. The NNA-dG covalent binding adduct could serve as such a biomarker, and play a role in identifying individuals exposed to THS, thus providing critical information for early detection and prevention.

Abstract: The invention relates to compounds of formula (I) wherein R1, R2, Y1, R4 and R5 are as defined herein. The compounds are intermediates in the synthesis of synthetic bile acid derivatives with pharmacological activity. The invention further provides methods related to the synthesizing of these intermediates, and methods of preparing obeticholic acid and obeticholic acid analogues from the compounds of the invention.

Abstract: The present invention discloses a process for the preparation of pregnadiene derivatives having formula I, their stereoisomer and intermediate thereof.

Abstract: The present invention refers to a method for binding a polycarboxylic acid to a solid phase. Further, the invention refers to a solid phase having a polycarboxylic acid immobilized thereto and methods of using the solid phase, e.g. for purifying His-tagged recombinant polypeptides.

Abstract: Disclosed herein are compounds for the treatment of neurodegenerative diseases and compositions comprising the same.

Abstract: Peptides with anti-influenza properties are disclosed herein. The peptides include dextro (D) or a mixture of dextro/levo (L)-amino acids, possess anti-influenza properties against multiple types of human influenza viruses along with the types which infect animals and birds and are useful as pharmaceutical compositions for the treatment or prevention of influenza virus infections.

Abstract: The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.

Abstract: Simple ?-hairpin peptides in linear and cyclic form that specifically bind to HIV-1 Trans-Activation Response element (HIV-1 TAR), as well as compositions and use thereof are described.

Abstract: Stable pre-fusion class I fusion proteins in the pre-fusion conformation, including one or more mutations in the hinge-loop that is present between the base helix and the RR1, are described.

Abstract: The present invention provides compositions comprising peptides derived from amino acid sequences (or from combinations thereof) of fusion and other protein regions of various viruses, including but not limited to, severe acute respiratory syndrome coronavirus, herpesvirus saimiri, human herpesvirus 6, Lassa virus, lymphocytic choriomeningitis virus, Mopeia virus, Tacaribe virus, Friend murine leukemia virus; human T lymphotropic virus type 1; herpesvirus ateles; Marburg virus; Sudan Ebola virus; Zaire Ebola virus, and comprising L- and/or D-amino acids and combinations thereof, which affect T cells by acting on the T cell antigen receptor (TCR). More specifically, the peptides act on the TCR??-CD3??-CD3??-?? signaling complex. Yet more specifically, the peptides act on the TCR?/CD3??/?? signaling module of TCR. The present invention further relates to the prevention and therapy of various T cell-related disease states involving the use of these compositions.

Abstract: The invention provides a peptide comprising: a core amino acid sequence, which is identical or similar to the amino acid sequence of a member of the Cecropin family. The invention further provides a nucleic acid sequence encoding the peptide and a vector comprising said nucleic acid. The invention further provides a pharmaceutical composition comprising said peptide or said nucleic acid. The invention further provides methods of treating an infection, overcoming inherent or acquired resistance of a microorganism to an antibiotic agent or disinfecting a wound, the methods comprises administering the peptide to a subject in need thereof.

Abstract: The present disclosure provides opsins, including variant opsins with increased activity and/or increased trafficking to the plasma membrane. The opsins are useful in therapeutic and screening applications, which are also provided.

Abstract: The present invention provides a peptide having anti-inflammatory activity. The present invention also provides the method of preparation of the peptide and compositions, and kits comprising the peptide. The invention further provides the method of treating inflammatory diseases employing the peptide of the present invention.

Abstract: The present invention provides for engineered molecular opsonins that may be used to bind biological pathogens or identify subclasses or specific pathogen species for use in devices and systems for treatment and diagnosis of patients with infectious diseases, blood-borne infections or sepsis. An aspect of the invention provides for mannose-binding lectin (MBL), which is an abundant natural serum protein that is part of the innate immune system. The ability of this protein lectin to bind to surface molecules on virtually all classes of biopathogens (viruses, bacteria, fungi, protozoans) make engineered forms of MBL extremely useful in diagnosing and treating infectious diseases and sepsis.

Abstract: The present invention relates to the use of Rspondins, particularly Rspondin2 (Rspo2) or Rspondin3 (Rspo3) or Rspondin nucleic acids, or regulators or effectors or modulators of Rspondin, e.g. Rspo2 and/or Rspo3 to promote or inhibit angiogenesis and/or vasculogenesis, respectively. The invention is based on the demonstration that Rspo3 and Rspo2 arc angiogenesis promoters, and the identification of Rspo2 and 3 as positive regulators of vascular endothelial growth factor (VEGF). These results indicate a major role for Rspondins, particularly Rspo3 and/or Rspo2 in the signaling system during angiogenesis. The invention also relates to the use of regulators or effectors or modulators of Rspondin3, including agonists and antagonists, in the treatment of conditions where treatment involves inhibiting or promoting angiogenesis and/or vasculogenesis.

Abstract: The present invention provides a novel peptide having bone formation-promoting effect and chondrocyte growth-promoting effect, in particular, a peptide having osteoblast growth-promoting activity, having 100 amino acid residues or less comprising an amino acid sequence selected from (a) Val-Asn-Pro-Glu-Ser-Glu-Glu-Glu-Asp-Glu-Ser-Ser-Pro-Tyr-Glu (SEQ ID NO: 1), (b) an amino acid sequence derived from the amino acid sequence (a) by conservative substitution or deletion of 1 to 3 amino acids, and (c) an amino acid sequence consisting of at least four contiguous amino acids of the amino acid sequence (a) or (b), or a derivative thereof or a salt thereof.

Abstract: This application relates to recombinant human interferon-like proteins. In one embodiment a recombinant protein created by gene shuffling technology is described having enhanced anti-viral and anti-proliferative activities in comparison to naturally occurring human inteferon like alpha 2b (HuIFN-?2b). The invention encompasses a polynucleotide encoding the protein and recombinant vectors and host cells comprising the polynucleotide. Preferably the polynucleotide is selected from the group of polynucleotides each having a sequence at least 93% identical to SEQ ID: No. 1 and the protein is selected from the group of proteins each having an amino acid sequence at least 85% identical to SEQ ID No: 2. The proteins and compositions comprising the proteins can be used for treatment of conditions responsive to interferon, therapy, such as viral diseases and cancer.

Abstract: Aspects of the disclosure provide fusion proteins that bind cells expressing one or more target molecules including, for example, one or more cell surface multisubunit signaling receptors (e.g., EGFRvIII-expressing cells that also express interferon receptors) and that induce anti-proliferative effects, and related compositions and methods for the treatment of cancer.

Abstract: The present invention relates to trigonal GLP-1/glucagon/GIP receptor agonists and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as for reduction of excess food intake.

Abstract: The present invention relates to compositions and methods for diagnosing and treating diseases, disorders or conditions associated with dysregulated expression of FSHR. The invention provides novel peptides that specifically bind to Follicle-stimulation hormone receptor (FSHR).

Abstract: The present invention relates to a fusion polypeptide containing a glucagon-like peptide (GLP) and an immunoglobulin hybrid Fc, and more specifically, to a fusion polypeptide with an increased half-life and improved efficacy compared to the conventional fusion polypeptide based on the discovery of an immunoglobulin hybrid Fc suitable for GLP or analogs thereof, and a pharmaceutical composition for treating diabetes, inflammatory bowel disease, endoenteritis or diarrhea caused by anticancer chemotherapy, or short bowel syndrome, containing the fusion polypeptide. The fusion polypeptide of the present invention has an increased half-life and improved resistance to DPP-4 enzyme compared to those of GLP-1 and GLP-2, and it thus has improved drug efficacy in treating diabetes, inflammatory bowel disease, endoenteritis or diarrhea caused by anticancer chemotherapy, or short bowel syndrome, compared to those of the conventional drugs.

Abstract: Disclosed are exosomes that include a packaging protein and a cargo RNA in which the packaging protein binds specifically to the cargo RNA. The packaging protein is a fusion protein that includes an RNA-binding domain and an exosome-targeting domain. The cargo RNA includes an RNA-motif that the RNA-binding domain of the fusion protein binds specifically such that the cargo RNA is packaged in the lumen of the exosomes.

Abstract: Compositions and methods are provided for modulating the activity of cells using engineered receptors, polynucleotide encoded engineered receptors, and gene therapy vectors comprising polynucleotides encoding engineered receptors. These compositions and methods find particular use in modulating the activity of neurons, for example in the treatment of disease or in the study of neuronal circuits.

Abstract: The present disclosure provides high affinity and enhanced affinity T cell receptors specific for human Wilms tumor protein 1 (WT-1) epitopes for use in treating diseases or disorders, such as cancer cells that overexpress WT-1.