Abstract: The present invention provides compounds useful as inhibitors of Tyrosine Kinase 2 (Tyk2), solid forms and compositions thereof, methods of producing the same, and methods of using the same in the treatment of Tyk2-mediated diseases.

Abstract: The present invention refers to novel process for the preparation of Apixaban. Further, the invention also related to a process for the preparation of intermediate of Apixaban from very basic and cheap row material i.e. Aniline which is widely commercially available. The present invention provides process for preparation of Apixaban using a different sequence of synthetic steps and does not involve use of Ullmann reaction.

Abstract: The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: The present invention relates to pyrazole fused-ring derivatives, their preparation methods, and use thereof in medicine. In particular, the present invention relates to a novel derivative represented by formula (I), and a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising the same and a method for preparing the same. The present invention also relates to use of the derivatives and the pharmaceutically acceptable salt thereof or the pharmaceutical composition comprising the same in the preparation of therapeutic agents, in particular Bruton tyrosine kinase inhibitors, and preparing a medicament for treating and/or preventing tumors and inflammatory associated diseases. The substituents on formula (I) are defined same as in the specification.

Abstract: Compounds that inhibit PI3K? activity, including compounds that selectively inhibit PI3K? activity, are disclosed. Methods of preparing such compounds are also disclosed, including the use of (S)-2-(1-aminopropyl)-5-fluoro-3-phenylquinazolin-4(3H)-one as a precursor to synthesize an exemplary compound disclosed in this application, (S)-2-(1-((9H-purin-6-yl)amino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K?) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which PI3K? plays a role in leukocyte function, using the compounds also are disclosed.

Abstract: Treatment of neurodegenerative diseases is achieved using small molecule purine scaffold compounds that inhibit Hsp90 and that possess the ability to cross the blood-brain barrier or are other wise delivered to the brain.

Abstract: The invention is directed towards stable formulations of 5,10-methylene-(6R)-tetrahydrofolic acid and its hemisulfate salt as well as pharmaceutical compositions and uses thereof in therapy, preferably chemotherapy.

Abstract: The present application provides processes for preparing (R)-4-(3-((S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one, which is useful as an inhibitor phosphoinositide 3-kinase-delta (PI3K?), as well as a salt form and intermediates related thereto.

Abstract: The present invention provides novel compounds described herein, such as of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

Abstract: The invention relates generally to compounds that modulate the activity of TGF?R-1 and TGF? R-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

Abstract: Provided is a compound of Formula (I) wherein the variable groups are defined herein.

Abstract: The present invention relates to crystal forms B, C and D of Ribociclib succinate salt and derivatives thereof, and their preparation method and composition. The crystal forms B, C and D of Ribociclib succinate salts are obtained by adding 7-cyclopentyl-N,N-dimethyl-2-(5-(piperain-1-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide solution into succinic acid solution for reaction, stirring the solution under high temperature, filtering the solution after cooling off.

Abstract: A fullerene derivative, used as a lubricant, includes, in a molecule: a fullerene backbone; and n pyrrolidine rings each being condensed to the fullerene backbone, each of the pyrrolidine rings including one aryl group including a group including m perfluoropolyether chains, “m” being an integer from 2 to 5 and “n” being an integer from 1 to 5.

Abstract: The present invention relates to a novel dihydropyranopyrimidinone derivative, a tautomer thereof, a stereoisomer thereof and their mixture, or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition for preventing or treating a tankyrase-related disease, which contains the same as an active ingredient.

Abstract: Enediyne compounds having a structure according to formula (I), where R1, R2, R3, R4, R5, R6, R7 and X are defined herein.

Abstract: Described herein are crystalline forms of Compound 1 useful for the prevention and treatment of angiogenic ocular conditions; methods of treating a disease comprising; processes for preparing; and kits comprising, the same.

Abstract: The present invention relates to 2-amino-4-arylpyrimidine and 2-amino-4-aryltriazine compounds as inhibitors of heat shock protein 90 family of chaperone proteins. The invention also features pharmaceutical compositions and kits that include the compounds and compositions of the invention. The invention further relates to the medical use of these compounds and compositions for the treatment of a disorder in a subject. For example, the disorder is a neurodegenerative disease.

Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract: The instant application relates to deazapurines, thienopyrimidines and furopyrimidines with zinc-binding moiety based derivatives and their use in the treatment of phosphoinositide 3-kinase related diseases and disorders such as cancer. The instant application further relates to the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

Abstract: The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CK1?, GSPT1, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.

Abstract: A bicarbazole compound represented by Formula 1: [Ar1]n1-(L1)a1-[Ar2]n2??Formula 1 wherein in Formula 1, a1, Ar1, Ar2, L1, n1, and n2 are the same as described in the specification.

Abstract: In one aspect, the invention relates to compounds having the formula: where R1-R6, a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

Abstract: The present invention relates to compounds of formula I: in which p, q, Y1, Y2, R1, R2a, R2b, R3a, R3b, R4a, R4b, R5a, R5b, R7 and R8 are defined in the Summary of the Invention; capable of inhibiting the activity of SHP2. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with the aberrant activity of SHP2.

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: This patent relates to invert water in oil (w/o) and water in silicone (w/si) emulsions made using non PEG/PPG containing polyhydric silicone emulsifiers. The polyhydric silicone polymers are based on allyl trimethylolpropane and pentaerythritol modified organic groups and do not contain any PEG and/or PPG groups (also known as polyethylene glycol and polypropylene glycols, polyethers, polyglycols,). These emulsions show improved emulsification stability and provide a light feel compared to emulsions made with other silicone based PEG/PPG compounds which are commonly used in the field.

Abstract: Compounds are generally provided, along with pharmaceutical compositions including such compounds. Methods are also generally provided for inhibiting ribose 5-phosphate isomerase in a human, such as via administering to the human the pharmaceutical composition that includes such a compound. Methods are also generally provided for treating a mammal that is infected by a parasitic organism, such as via administering to the mammal the pharmaceutical composition that includes such a compound. Methods are also generally provided for forming a pharmaceutical composition.

Abstract: The disclosure provides compounds having formula (I): and the pharmaceutically acceptable salts thereof, wherein R1, R2, R2?, and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON). The disclosure also provides compounds having formula (I) for use in treating cancer.

Abstract: Gold(I) complexes and gold(I) dithiocarbamate polymers as anticancer therapeutics. The Au(I) ion within the gold(I) complexes is coordinated to two phosphine ligands. The repeating unit formed by Au(I) ion coordinating to dithiocarbamate ligands are connected by Au(I)-Au(I) interactions within the gold(I) dithiocarbamate polymers. Also disclosed are methods of synthesis, pharmaceutical compositions incorporating the gold(I) complexes, pharmaceutical compositions incorporating the gold(I) dithiocarbamate polymers, and methods of treating cancer.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5 is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: Highly active, recoverable and recyclable transition metal-based metathesis catalysts and their organometallic complexes including dendrimeric complexes are disclosed, including a Ru complex bearing a 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene and styrenyl ether ligand. The heterocyclic ligand significantly enhances the catalytic activity, and the styrenyl ether allows for the easy recovery of the Ru complex. Derivatized catalysts capable of being immobilized on substrate surfaces are also disclosed. The present catalysts can be used to catalyze ring-closing metathesis (RCM), ring-opening (ROM) and cross metatheses (CM) reactions, and promote the efficient formation of various trisubstituted olefins at ambient temperature in high yield.

Abstract: Provided is a cobalt complex which is useful for the production of a cobalt-containing thin film under conditions where no oxidizing gas is used. A cobalt complex represented by general formula (1) (wherein R1 represents a silyloxy group represented by general formula (2) (wherein R6, R7 and R8 independently represent an alkyl group having 1 to 6 carbon atoms); R2 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or a silyloxy group represented by general formula (2); R3, R4 and R5 independently represent a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; and L represents a diene having 4 to 10 carbon atoms) is used.

Abstract: A novel catalyst capable of selectively catalyzing conversion from glucose to fructose in water or in an aqueous solution is provided. The catalyst is a solid catalyst for a hydride isomerization reaction from glucose to fructose performed in water or in an aqueous solution, comprising a group 13 element oxide whose surface has been subjected to a phosphoric acid treatment.

Abstract: The present disclosure relates to novel modular methods for generating a diversity of N-glycans of high mannose, hybrid and complex types. The present disclosure also relates to exemplary arrays of the synthesized N-glycans spotted onto aluminium oxide coated slides. These arrays can be used to detect and analyze binding interactions between the synthesized N-glycans and glycan binding molecules, such as HIV-1 neutralizing antibodies. The present disclosure also relates to methods for identifying agents that bind to various types of molecules on the arrays and to defining the structural elements of the molecules on the arrays that bind to those agents. The arrays and methods provided herein may be used for general epitope identification, drug discovery and as analytical tools. The present disclosure also provides useful glycans and epitope determinants that are useful in detecting, diagnosing, recurrence monitoring and preventing pathological diseases such as HIV.

Abstract: The present invention provides methods, compositions, mixtures and kits utilizing deoxynucleoside triphosphates comprising a 3?-O position capped by a group comprising methylenedisulfide as a cleavable protecting group and a detectable label reversibly connected to the nucleobase of said deoxynucleoside. Such compounds provide new possibilities for future sequencing technologies, including but not limited to Sequencing by Synthesis.

Abstract: Cyclic-GMP-AMP synthase (cGAS) and cyclic-GMP-AMP (cGAMP), including 2?3-cGAMP, 2?2-cGAMP, 3?2?-cGAMP and 3?3?-GAMP, are used in pharmaceutical formulations (including vaccine adjuvants), drug screens, therapies and diagnostics.

Abstract: This disclosure relates to progesterone derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation resulting from traumatic brain injury or stroke.

Abstract: The described invention provides a method for treating myocardial infarction (MI) in a subject comprising administering to the subject a therapeutic amount of a pharmaceutical composition comprising a polypeptide of amino sequence YARAAARQARAKALARQLGVAA (SEQ ID NO: 1) or a functional equivalent thereof made from a fusion between a first polypeptide that is a cell permeable protein (CPP) selected from the group consisting of a polypeptide of amino acid sequence YARAAARQARA (SEQ ID NO: 2), WLRRIKAWLRRIKA (SEQ ID NO: 21), WLRRIKA (SEQ ID NO: 22), YGRKKRRQRRR (SEQ ID NO: 23), FAKLAARLYR (SEQ ID NO: 25), and KAFAKLAARLYR (SEQ ID NO: 26), and a second polypeptide that is a therapeutic domain (TD), and a pharmaceutically acceptable carrier. The described invention also provides a kit comprising a composition comprising at least one MK2 inhibitor peptide; a means for administering the composition; and a packaging material.

Abstract: The invention provides peptides that can reactivate p53 mutants efficiently and specifically, as well as methods that allow the identification, selection and isolation of such peptides, in a precise, cost and time effective manner. In particular, there are provided mutant p53 reactivating peptides that can restore the native wild type p53 folding, and hence the tumor suppressor activity, to the mutant p53 protein. Such peptides are useful for treating various conditions and diseases in which p53 is mutated.

Abstract: Disclosed herein are novel anti-microbial peptides with inhibitory activity against M. tuberculosis and streptococcus bacteria. Additionally, a method for designing novel anti-microbial peptides is disclosed.

Abstract: The present invention belongs to the field of functional proteomics and more particularly to the field of protein aggregation. The invention discloses a method for interfering with the function of a target protein and uses a non-naturally, user-designed molecule, designated as interferor, that has a specificity for a target protein and which induces aggregation upon contact with said target protein. The present invention also discloses such interferor molecules and their use in agrobiotech applications.

Abstract: The invention relates to a peptide dendrimer described by a general formula X—(B2—[Y2]S-D1)2-B1—Z, wherein X is (D2)4 or (D3)8-(B3—[Y3]r-D2)4 or a higher analog, Y is a linkage moiety, Z is a central moiety; each B denotes a diaminoalkylcarboxylic acid moiety; each D is a hydrophobic or cationic amino acid, or a di- or tripeptide composed of hydrophobic and cationic amino acids, for use as a pharmaceutical.

Abstract: The present invention relates to, in part, compositions comprising improved flagellin derived constructs and methods of using for vaccination, including adjuvants comprising flagellin-based agents.

Abstract: Knockout of the meningococcal mltA homolog gives bacteria that spontaneously release vesicles that are rich in immunogenic outer membrane proteins and that can elicit cross-protective antibody responses with higher bactericidal titres than OMVs prepared by normal production processes. Thus the invention provides a bacterium having a knockout mutation of its mltA gene. The invention also provides a bacterium, wherein the bacterium: (i) has a cell wall that includes peptidoglycan; and (ii) does not express a protein having the lytic transglycosylase activity MltA protein. The invention also provides compositions comprising vesicles that, during culture of bacteria of the invention, are released into the culture medium.

Abstract: The invention discloses microorganism cell culture conditions that result in increased cellular and media concentrations of a biological pigment. The invention has applications in use as a natural food coloring, as antioxidants in the food supplement industries, in the nutraceutical, pharmaceutical, and cosmeceutical industries, and a non-toxic ink. The method results in pigment that is relatively easy to separate from the microorganism culture.

Abstract: A system, including methods and compositions, for treatment of ischemia.

Abstract: Disclosed are recombinant polypeptides that include (a) a filaggrin amino acid sequence and (b) a cell importation signal sequence that includes a motif of two to fifteen amino acids, wherein the motif includes at least one arginine residue and at least one methionine residue. Also disclosed are nucleic acids encoding the recombinant polypeptides of the present invention, and compositions that include the recombinant polypeptides and nucleic acids of the present invention. Methods of treating or preventing a skin disease or skin disorder using the compositions of the present invention are also included, as well as kits that include a sealed containing that includes a recombinant polypeptide of the present invention.

Abstract: GDF15 polypeptides, constructs comprising GDF15, and mutants thereof are provided. In various embodiments the GDF15 polypeptides, constructs comprising GDF15, and mutants thereof, can be of use in the treatment or ameliorating a metabolic disorder. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy.

Abstract: The present invention provides FGF-2 polypeptides that differ from the wild-type FGF-2 (SEQ ID NO:1) at least at amino acid position 56, 102 and 119, wherein the differences are Q56I, N102G, K119N substitutions, leading to FGF-2 polypeptides with higher thermostability, higher biological activity and higher resistance to proteolytic degradation. These polypeptides can be used in cell culture media.

Abstract: The invention relates to a polypeptide selected from bone morphogenetic protein 10 (BMP10), or a bone morphogenetic protein 9 (BMP9) variant lacking osteogenic activity, for use in the treatment of a vascular disease or a respiratory disease. The invention also relates to novel BMP9 variants and to pharmaceutical compositions comprising said polypeptides.

Abstract: The present invention provides a fusion protein, comprising a chemokine polypeptide, which is a chemokine or a receptor binding domain thereof; and a cytokine polypeptide connected to said chemokine polypeptide, which is an interleukin, a TNF-superfamily cytokine or a receptor-binding domain thereof; wherein the chemokine polypeptide and the cytokine polypeptide have a common target cell, and the fusion protein has an improved chemokine activity as compared to the chemokine polypeptide, and an improved cytokine activity as compared to the cytokine polypeptide.