Abstract: Disclosed are compounds useful as inhibitors of the Wnt signalling pathway. Specifically, inhibitors of Porcupine (Porcn) are contemplated by the invention. In addition, the invention contemplates processes to prepare the compounds and uses of the compounds. The compounds of the invention may therefore be used in treating conditions mediated by the Wnt signalling pathway, for example, in treating cancer, sarcoma, melanoma, skin cancer, haematological tumors, lymphoma, carcinoma, and leukemia; or enhancing the effectiveness of an anti-cancer treatment.

Abstract: A compound of formula (I): wherein R is H or F; or a salt thereof.

Abstract: A process for preparing halogenated azaindole compounds makes use of stable reagents including a brominating reagent, a boroxine and a sulfonic anhydride to enhance the selectivity and yield of the final product. In addition, the process is associated with various other advantages, including the ability to recycle reagents, cost reduction, and improved manufacturability.

Abstract: The present invention pertains generally to the field of organic chemical synthesis, and in particular to certain methods for the synthesis of 8-(4-aminophenyoxy)-4H-pyrido[2,3-b[pyrazin-3-one and related compounds (denoted herein as (3)) from 4-(4-aminophenyoxy)pyridine-2,3-diamine and related compounds (denoted herein as (1)), by reaction with glyoxylic acid (denoted herein as (2)). The compounds (3) are useful in the synthesis of known anti-cancer agents, such as 1-(5-tert-butyl-2-(4-methyl-phenyl)-pyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyflurea.

Abstract: The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 1-(5-tert-butyl-2-aryl-pyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea compounds (referred herein as “TBAP compounds”) that, inter alia, inhibit RAF (e.g., BRAF, CRAF, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF, CRAF, etc.); and to treat disorders including: proliferative disorders; cancer (including, e.g., malignant melanoma, colorectal carcinoma, pancreatic adenocarcinoma); inflammation; immunological disorders; viral infections; fibrotic disorders; disorders associated with a mutated form of RAF (e.g., BRAF, CRAF, etc.); disorders ameliorated by the inhibition of RAF (e.g., BRAF, CRAF, etc.

Abstract: The invention provides novel compounds having the general formula: wherein R1, R2, R3, Q, U,W, Z, X and Y are as described herein, compositions including the compounds and methods of using the compounds. These compounds are HbsAg inhibitors and are useful as medicaments for the treatment or prophylaxis of HBV infection.

Abstract: The present invention relates to compounds which bind to the NR1H4 receptor (FXR) and act as agonists of FXR. The invention further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds and to a process for the synthesis of said compounds.

Abstract: Described herein are compounds that inhibit ALK2 and its mutants, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions.

Abstract: Disclosed is a novel chiral synthesis of N-acyl-(3-substituted)-(8-substituted)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazines of Formula (I), avoiding the use of protection/deprotection steps.

Abstract: The present invention relates to a salt form of a benzodiazepine derivative, in particular crystalline solid state forms, to pharmaceutical compositions comprising the same and to its use in therapy.

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

Abstract: Provided herein are solid forms (e.g., salts, co-crystals, amorphous forms, and crystalline forms) of methyl (R)-2-(2-(2-chloro-5-(2-hydroxy-3-(methylamino)propoxy)phenyl)-6-(3,5-dimethylisoxazol-4-yl)-5-methylpyrimidin-4-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate (compound 109-3). Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve the solid forms for inhibiting the activity of co-activator-associated arginine methyltransferase 1 (CARM1) and for treating CARM1-mediated disorders (e.g., proliferative disorders and metabolic disorders).

Abstract: This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung c

Abstract: A compound of formula I wherein: n is 1 or 2: p is 0 or 1; R1 is optionally one or more halo or methyl groups; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted C5-12 heteroaryl.

Abstract: The present invention relates to compounds of formula I shown below: wherein Q is as defined herein. The compounds of formula I act as selective positive allosteric modulators of strychnine-sensitive alpha 1-glycine receptors. The present invention further relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of diseases or conditions in which strychnine-sensitive alpha 1-glycine receptor activity is implicated (such as, for example, chronic pain. The present invention also relates to processes for the preparation of these compounds and to pharmaceutical compositions comprising them.

Abstract: The invention relates to heterocyclic compounds with benzo[c]coumarin structures and to electronic devices, in particular organic electroluminescent devices, containing said compounds.

Abstract: In general, the present invention features improved methods useful for the synthesis of analogs of halichondrin B, such as eribulin and pharmaceutically acceptable salts thereof (e.g., eribulin mesylate).

Abstract: This invention relates to thieno[3,2-d]pyrimidines derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.

Abstract: Disclosed are aminosulfonyl-based compounds represented by the general formula I or tautomers, enantiomers, racemates or pharmaceutically acceptable salts thereof, a method for preparing the same, pharmaceutical compositions and uses thereof. The compounds can be used to treat epilepsy, convulsions, obesity and the like.

Abstract: A compound represented by the general formula (I) [R1 represents a C1-6 alkyl group, a halogen atom, or the like; A represents a phenylene group, or the like; X represents —CH(R3)—, —O—, —NH—, or the like; Y represents —O—, —NH—, —N?, or —S—; . . . represents a single bond or double bond; n represents 1 to 3; R2 represents a C1-6 alkyl group, a C1-6 alkoxy group, or the like; and R3 represents hydrogen atom, a C1-6 alkyl group, or the like], or a salt thereof which has a blood LDL cholesterol-reducing action, and is useful as an active ingredient of medicaments.

Abstract: The disclosure relates to compounds of formula (I) useful in the treatment of tauopathies and Alzheimer's disease wherein A, R, W, Q, n, and m are described herein.

Abstract: The present invention relates to novel immunostimulatory molecules which are derived from the intestinal protozoan Entamoeba histolytica. The compounds have been found to be useful for enhancing and/or inducing an immune response in a subject in need thereof. Specifically, the compounds have been found to be useful for the treatment of cancer diseases, such as breast cancer, and parasitic diseases, such as leishmaniasis. The invention also provides pharmaceutical compositions comprising the novel compounds.

Abstract: Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein R12 or R13 on the A group is an amide substituent (R32) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

Abstract: Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein R12 or R13 on the A group is a carbamate, ester, or ketone substituent (R32) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

Abstract: This invention provides compounds, compositions and methods for modulating the expression of human p21 using RNA interference. The RNA interference molecules can be used in methods for preventing or treating diseases such as malignant tumor. Provided are a range of siRNA structures, having one or more nucleotides being modified or chemically-modified. Advantageous structures include siRNAs with 2?-deoxy nucleotides located in the seed region, as well as other nucleotide modifications.

Abstract: Provided are an L-proline complex of a sodium-glucose cotransporter 2 inhibitor, and a monohydrate and a crystal of the L-proline complex. Specifically, provided are 1,6-dehydrated-1—C{4-chloro-3-[(3-fluoro-4-ethoxyphenyl)methyl]phenyl}-5—C-(hydroxymethyl)-?-L-idopyranose L-proline (a compound of formula (I)), a monohydrate and a type A crystal thereof, and a preparation method therefor. The obtained type A crystal of the compound of formula (I) has good chemical stability and crystal stability, and the crystallization solvent used has low toxicity and low residue, so the type A crystal can be better used in clinical treatment.

Abstract: The present disclosure describes nucleoside and nucleoside analogues that are conjugated to a vitamin E derivative via a phosphate ester or a phosphoramidate linkage. The nucleoside or nucleoside analogues can provide enhanced therapeutic activity (e.g., antiproliferative activity against tumor cells) and/or greater chemical stability in aqueous solutions.

Abstract: The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Abstract: The present invention provides novel methods to treat disease by modulating retinoid-related orphan receptor gamma (ROR-gamma) in vitro and in vivo with ursolic acid analogs, and compositions thereof. The methods and compounds disclosed herein are useful for inhibiting the differentiation of a population of T cells, or treating a disease related to Th17 cell responses in a subject. Examples of such diseases include, but are not limited to, autoimmune diseases, multiple sclerosis, rheumatoid arthritis, psoriasis and diabetes.

Abstract: The present invention refers to new species of an ion exchange adsorber which is suitable for the separation of host cell proteins (HCPs), antibody fragments and low molecular weight substances from solutions containing antibodies. The invention especially refers to a process for purifying biological samples by separating biomolecules of interest and impurities, comprising steps of contacting a sample with said chromatography media consisting of fibers, said fibers having imparted thereon functionality enabling ion exchange chromatography and/or hydrophobic interaction.

Abstract: A functionalized fine fiber is provided. In an embodiment, the functionalized fine fiber is usable in chromatography. The functionalized fine fiber includes a matrix of fine fiber. The fine fibers preferably have an average diameter of less than 2 micron, and each fine fiber preferably has a length of at least 1 millimeter. The fine fibers carry and immobilize functional molecules.

Abstract: Novel methods for preparation of Carfilzomib and intermediates thereof with high stereo selection are reported. The synthetic procedures result in substantially pure Carfilzomib (I).

Abstract: This application describes a family of compounds acting as ?-arrestin effectors. Such compounds may provide significant therapeutic benefit in the treatment of chronic and acute cardiovascular diseases.

Abstract: A method of treating an IL-17 mediated disease in a subject by administering to the subject a therapeutically effective amount of a of a cell-permeable decoy peptide that competitively inhibits binding of the SEFIR domain of IL-17R to the SEFIR domain of Act1. In particular, it has been determined that the ?C helix region of the SEFIR domain of both IL-17R and Act1 plays an important role in the association of IL-17R and Act1. To facilitate cell permeation, the decoy peptide is preferably conjugated to a protein transduction domain. Examples of IL-17 mediated diseases include various human and animal inflammatory and autoimmune diseases such as asthma.

Abstract: The present invention described herein relates to the composition that interact with molecules that suppress the immune system.

Abstract: The invention provides for novel peptide derivatives and compositions comprising the same. The invention further provides methods of treatment comprising administering novel peptide derivatives and/or compositions comprising the same.

Abstract: Disclosed are a conotoxin polypeptide ?-CPTx-bt104, a method for preparation thereof, and an application thereof. The conotoxin polypeptide of the present invention consists of 11 amino acids, has a molecular weight of 1313.47 daltons, and has the full sequence SLCCPEDRWCC (SEQ. ID NO. 1).

Abstract: The present invention provides biologically active peptidomimetic macrocycles with improved properties relative to their corresponding polypeptides. The invention additionally provides methods of preparing and using such macrocycles, for example in therapeutic applications.

Abstract: Novel antiviral polypeptides are disclosed along with methods for their use to interfere with viral replication cycles by substantially impairing the binding of viruses to target cells, viral replication and assembly in infected cells, and viral egress from infected cells including viral lysis of host cells. The present antiviral peptides exhibit broad specificity across a range of human viral pathogens by virtue of their derivation from selected viral resistance genes and their ability to interfere with conserved mechanisms of host cell-virus interactions.

Abstract: Disclosed are immunogens including a recombinant RSV F protein stabilized in a prefusion conformation. Also disclosed are nucleic acids encoding the immunogens and methods of producing the immunogens. Methods for generating an immune response in a subject are also disclosed. In some embodiments, the method is a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the immunogen to the subject.

Abstract: Nutritive proteins are provided. In some embodiments the nutritive proteins comprise at least one of a level of a) a ratio of branch chain amino acid residues to total amino acid residues present in the nutritive protein equal to or greater than the ratio of branch chain amino acid residues to total amino acid residues present in whey protein; b) a ratio of leucine residues to total amino acid residues present in the nutritive protein equal to or greater than the ratio of leucine residues to total amino acid residues present in whey protein; and c) a ratio of essential amino acid residues to total amino acid residues present in the nutritive protein equal to or greater than the ratio of essential amino acid residues to total amino acid residues present in whey protein.

Abstract: Disclosed are a conotoxin polypeptide ?-CPTx-bt105, a method for preparation thereof, and an application thereof. The conotoxin polypeptide of the present invention consists of 16 amino acids, has a molecular weight of 1626.62 daltons, and has the full sequence GICCVDDTCTTHSGCL (SEQ. ID NO. 1).

Abstract: Disclosed are a conotoxin polypeptide ?-CPTx-bt103, a method for preparation thereof, and an application thereof. The conotoxin polypeptide of the present invention consists of 29 amino acids, has a molecular weight of 3141.43 daltons, and has the full sequence RTNCGETCLKDEQCVGACQICVPSQLKCL (SEQ ID NO. 1).

Abstract: Methods of using an ETB receptor agonist, such as IRL-1620, for the treatment of stroke or cerebrovascular accidents are disclosed. The ETB receptor agonist is used alone or in combination with a second agent useful in the treatment of stroke or other cerebrovascular accident.

Abstract: Compositions containing multivalent and monovalent multispecific complexes having scaffolds such as antibodies that support such binding functionalities are described. The use of and methods of compositions containing multivalent and monovalent multispecific complexes having scaffolds, such as antibodies, that support such binding functionalities are also described.

Abstract: The present disclosure describes a new native peptide designated herein as Dwarf Open Reading Frame, or DWORF. This peptide enhances the apparent activity of the SERCA pump, is positively inotropic and lusitropic, and therefore is provided as a therapeutic agent for disorders characterized by cytosolic calcium overload.

Abstract: The present invention provides nucleic acids encoding a fusion protein comprising a nucleotide sequence encoding GRIM-19 or a biologically active fragment or derivative thereof and a nucleotide sequence encoding a protein transduction domain. Proteins encoded by the nucleic acids, pharmaceutical compositions and methods of treatment are also provided. The invention also provides viral vectors comprising GRIM-19 or a biologically active fragment or derivative thereof, pharmaceutical compositions and methods of treatment using the same.

Abstract: The object is to provide a tumor antigen peptide that is specifically presented on a cancer and a cancer stem cell, and a pharmaceutical composition, etc. that is useful for the prevention and/or treatment of a cancer and contains the above peptide as an active ingredient. The above object has been accomplished by providing a BORIS-derived partial peptide belonging to isoform A or C or subfamily 5 or 6, a polynucleotide encoding the peptide, a pharmaceutical composition containing the above as an active ingredient, and an agent for the prevention and/or treatment of a cancer, the agent containing the above as an active ingredient and inducing CTLs.

Abstract: In general, the invention features substantially purified MANF and substantially purified nucleic acids encoding the same. The invention also features a pharmaceutical composition that includes MANF and a pharmaceutically-acceptable excipient, methods for treatment of a neurodegenerative disease, methods for improving dopaminergic neuronal survival during or following cell transplantation, methods for production of neurons for transplantation, and methods for identifying compounds that modulate or mimic MANF's biological activity.

Abstract: The present application discloses in detail mutant ligands of the human G protein alpha-subunit—G?i1—, wherein at least one amino acid residue has been replaced with alanine if the at least one amino acid residue is a non-alanine residue, or at least one amino acid residue has been replace with glycine if the at least one amino acid residue is alanine and wherein the at least one amino acid residue is comprised in a first group containing of the amino acid residues with position R32A, K54A, I55A, I56A, H57A, R176A, E245A, Y296A, T327A, N331A, V332A and D350A or is comprised in a second group containing G42A, A59G, T177A, D200A, A226G, E297A, A300G and F334A or is comprised in a third group containing V50A, A59G, R178A 30 and K180A.