Abstract: There is provided compounds of formula I, wherein R1, R2, R3 R4, R5, R6, R7a and R7b have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. CDK8 and/or Haspin kinase) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

Abstract: The present invention provides a nucleator composition comprising sorbitol acetal, sorbitol diacetal, and sorbitol triacetal. The nucleator composition can improve the nucleation performance of a polymer, increase transparency, glossiness, flexural modulus and tensile strength of polymer films, polymer sheets and polymer molding articles, and increase heat distortion temperature and dimensional stability of polymer articles.

Abstract: The present invention discloses a novel process for the preparation of macrocyclic ketone analogs of halichondrin B or pharmaceutically acceptable salts thereof and to novel intermediates which are produced during the course of carrying out the novel process.

Abstract: The present invention relates to compounds and methods which may be useful as inhibitors of HIF pathway activity for the treatment or prevention of cancer and other hypoxia-mediated diseases.

Abstract: The present invention concerns compounds of formula I or a pharmaceutically acceptable salt thereof which inhibit HIF prolyl hydroxylase, their use for enhancing endogenous production of erythropoietin, and for treating conditions associated with reduced endogenous production of erythropoietin such as anemia and like conditions, as well as pharmaceutical compositions comprising such a compound and a pharmaceutical carrier.

Abstract: The invention provides tetrahydro[1,8]naphthyridine and related compounds, pharmaceutical compositions, methods of promoting ROR activity, increasing the amount of IL-17 in a subject, and treating cancer using such tetrahydro[1,8]naphthyridine and related compounds.

Abstract: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR13—C1-5alkyl-, —C1-5alkyl-NR14—CO—C1-5alkyl-, —C1-2alkyl-NR21—H2—CO—NH—C1-3alkyl- or —C1-2alkyl-NR23—CO—CR16R17—NH—; X1 represents O or —O—C1-2alkyl-; X2 represents a direct bond, C1-2alkyl, —CO—C1-2alkyl or NR12—C1-2alkyl; R1 represents hydrogen or halo; R2 represents halo, acetylene or Het1 R3 represents hydrogen or cyano; R4 represents Ar4—C1-4alkyloxy-, C1-4alkyloxy- or C1-4alkyloxy substituted with one or where possible two or more substituents selected from Het2, NR7R8, hydroxy and C1-4alkyloxy-C1-4alkyloxy-; R7 represents hydrogen or C1-4alkyl; R8 represents C1-4alkyl substituted with NR25R26 or C1-4alkylsulfonyl; R12 represents hydrogen or C1-4alkyl-; R13 represents Ar6-sulfonyl or C1-6alkyloxycarbonyl optionally substituted with phenyl; R16 and R17 represents hydr

Abstract: The present invention provides compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same. Specifically, bicyclic heteroaryl derivatives containing a imidazole, thiazole or oxazole fused to a pyridinone, pyrimidinone or pyrimidindione are provided. These compounds have therapeutic utility toward treating an ACC enzyme mediated disorder such as obesity in a subject, upon administration in an effective amount to said subject.

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 chronic kidney disease and conditions associated with excessive salt and water retention.

Abstract: Crystalline free bases and crystalline acid salts of 9-((8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)thio)-4-methyl-2H-[1,4]oxaazido[3,2-c]quinoline-3(4H)-one are disclosed as C-Met inhibitors. Their preparation methods and uses are also described. In particular, crystal forms I, II, III and IV of the free base; crystal form I of the hydrochloride salt; crystal forms I and II of the sulfate salt; crystal forms I, II, III and IV of the phosphate salt; crystal forms I, II, III, IV and V of the mesylate salt; crystal forms I, II and III of the p-toluenesulfonate salt; and crystal forms I, II and III of the 1,5-naphthalenedisulfonate salt are disclosed. Also disclosed are methods for preparing the above-mentioned crystal forms, pharmaceutical compositions thereof, methods for regulating the catalytic activity of a protein kinase, and methods of treating protein kinase-related diseases.

Abstract: This disclosure provides novel imidazopyridazine compounds of formula (I) and pharmaceutical acceptable salt thereof, pharmaceutical compositions containing them, a process for preparing them, and their practical effect in inhibiting PI3K and potential use in treating a disease responsive to inhibition of PI3K, for example, an inflammatory disease, autoimmune disease or cancer.

Abstract: The present invention provides compounds of formula (I) wherein A, X, Y, R1 and R2 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.

Abstract: The present invention provides compounds of Formula (Ia): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt 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: A process is provided for precise self-assembly and re-arrangement of a three-dimensional terpyridine-based coordination complex. A plurality of terpyridine-containing ligands are reacted with at least one metal ion, in a pre-selected molar ratio, to form a self-assembled three-dimensional terpyridine-based coordination complex having a first configuration. A triggering event, such as exposure to light or dilution, causes the coordination complex to re-arrange to form at least two smaller, substantially identical, three-dimensional terpyridine-based coordination complexes, each having a second configuration that is different from the first configuration. Upon application of a second triggering event, such as concentration, the re-arrangement is reversed.

Abstract: The present disclosure relates, in exemplary embodiments, to compositions of matter comprising synthetic blends of at least two feedstocks that produce a distribution of fluorinated polyhedral oligomeric silsesquioxane molecule structures. The present disclosure also relates, in exemplary embodiments, to methods of making such synthetic blends.

Abstract: The present invention relates to a method for treating ocular inflammatory diseases in a subject in need of such treatment, which comprises administering a pharmaceutical composition comprising a therapeutically effective amount of at least one agonist of Formyl peptide receptor 2.

Abstract: Described herein is an enzyme-mediated approach to bioconjugation at nanoparticle (NP) surfaces. This process is enabled by a new synthetic linker compatible with the covalent attachment of alkyne modified substrates, including dyes, peptides and nucleic acids. The methods described herein specifically allow for the linkage of molecules to a DNA-functionalized nanoparticle surface. Enzymatic ligation of molecules to the terminal hydroxyl group of DNA using T4 DNA ligase is achieved through incorporation of a single monophosphate on the approaching substrate. In contrast to previous strategies, the linkers disclosed herein are compatible with alkyne modified molecules of a variety of sizes and charges indicating that the ligase minimally requires the monophosphate and the incoming hydroxyl for conjugation to be successful.

Abstract: Disclosed is a solution comprising the chloride hydrochloride salt of 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium (fosnetupitant) and palonosetron hydrochloride in combination with dexamethasone and its application in methods for preventing acute and delayed nausea and vomiting in a human patient receiving highly emetogenic cancer chemotherapy.

Abstract: Disclosed embodiments concern novel interleukin receptor associated kinases (IRAK) inhibitors and compositions comprising such inhibitors. Also disclosed are methods of making and using the compounds and compositions. The disclosed compounds and/or compositions may be used to treat or prevent an IRAK-associated disease or condition.

Abstract: Disclosed embodiments concern novel interleukin receptor associated kinases (IRAK) inhibitors and compositions comprising such inhibitors. Also disclosed are methods of making and using the compounds and compositions. The disclosed compounds and/or compositions may be used to treat or prevent an IRAK-associated disease or condition.

Abstract: The present invention provides novel and improved processes for treating a lignocellulosic biomass or technical lignin using ionic liquids to obtain lignin breakdown products and polysaccharide biomass components. Recycling of ionic liquids can be included in the methods of the invention.

Abstract: A compound having the formula I: is disclosed. A method of preparing the compound of formula I is also disclosed.

Abstract: A compound having the following formula I: is disclosed. A method of preparing the compound of formula I is also disclosed.

Abstract: This invention relates to methods of stimulating the activity of the human and animal enteric nervous system. The method comprises orally administering an aminoserol, such as squalamine, a naturally occurring aminosterol isolated from Squalus acanthias, or derivatives thereof, to a subject in need.

Abstract: This invention relates to methods of stimulating the activity of the human and animal enteric nervous system. The method comprises orally administering an aminoserol, such as squalamine, a naturally occurring aminosterol isolated from Squalus acanthias, or derivatives thereof, to a subject in need.

Abstract: The present invention provides compounds of Formula I, pharmaceutical compositions comprising these compounds and methods of using these compounds to prevent or treat FXR-mediated or TGR5-mediated diseases or conditions.

Abstract: The present invention relates to a terpenoid derivative that has the ability to activate the Keap1/Nrf2/ARE signaling pathway and is excellent in anti-inflammatory action and cytoprotective action, and a sustained-release pharmaceutical composition effective for the treatment and prevention of a posterior eye disease caused by oxidative stress, comprising the terpenoid derivative as an active ingredient. The present invention provides a local administration-type sustained-release pharmaceutical composition for the treatment or prevention of a posterior eye disease, comprising the terpenoid derivative of the present invention as an active ingredient, wherein the sustained-release pharmaceutical composition maintains a pharmacological action thereof for 1 week or longer by the sustained release of the terpenoid derivative under physiological conditions and has a base material administrable to the vitreous body and a form administrable to the vitreous body.

Abstract: Novel homo-aza-steroidal esters with alkylating bis(2-chloroethyl)aminophenoxy propanoic acid and substituted derivatives, processes for their preparation, pharmaceutical compositions containing them and use thereof in the treatment of cancer.

Abstract: The present invention provides means and methods for equipping a polypeptide of interest at its C-terminus with a versatile adaptor amino acid that allows the functionalization of the polypeptide of interest.

Abstract: The present invention relates to decoy peptide or polypeptide consisting of a peptide sequence represented by the following Formula I: X1-Ala-X2—X3-Ile-Glu-X4 (I). It is noteworthy that the decoy peptide or polypeptide of the present invention significantly elevates phosphorylation levels of PLB by inhibiting PP1-mediated dephosphorylation. In addition, the decoy peptide or polypeptide provides cardio-protective effects by restoring of SERCA2a activity and inotropic effect of enhancing myocardial contractility. The present invention will contribute greatly to the prevention or treatment of diseases associated with PLB.

Abstract: Compositions and methods are provided for eliciting antigen-specific T-cell responses against human cyclin A1 (CCNA1), which is herein identified as a leukemia-associated antigen based on its overexpression in acute myeloid leukemia (AML) including leukemia stem cells (LSC) and in immunologically privileged testis cells, but not in other normal cell types. CCNA1-derived peptide epitopes that are immunogenic for T-cells including CTL are disclosed, as are immunotherapeutic approaches using such peptides for vaccines and generation of adoptive transfer therapeutic cells.

Abstract: The present invention relates to dual-site BACE1 inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

Abstract: The present invention discloses the applications of a low molecular polypeptide ZY4 in preparing drugs for anti-acnes, anti-infection, anti-cancer and cosmetics. The low molecular polypeptide ZY4 comprises 17 amino acid residues, with a molecular weight of 2374.0 Da, an isoelectric point of 10.74, and an amino acid sequence of SEQ ID NO:1. The low molecular polypeptide ZY4 in the invention is artificially synthesized, with the advantages of small molecular weight and convenient artificial synthesis. The experiments have showed that the polypeptide ZY4 has obvious antibacterial effect and has significant therapeutic effect on acnes. The polypeptides can inhibit the growth of tumor cells and kill the tumor cells. The low molecular polypeptide ZY4 can be used in the preparation of medicaments or cosmetics having the effect of anti-infective, anti-tumor or anti-acne.

Abstract: The present invention provides modulators of complement activity. Also provided are methods of utilizing such modulators as therapeutics.

Abstract: The invention relates to agents and to pharmaceutical compositions for reducing the formation of amyloid and/or for promoting the disaggregation of amyloid proteins. The compositions may also be used to detect amyloid.

Abstract: A kappa light chain-binding polypeptide comprising or consisting essentially of one or more binding domains of Peptostreptococcus Protein L, each of said domains being selected from the group consisting of domain 2, domain 3 and domain 4.

Abstract: The invention discloses kappa light chain-binding polypeptide comprising a mutated binding domain of Peptostreptococcus protein L, wherein at least one asparagine residue of a parental domain defined by, or having at least 95% or 98% sequence homology with, SEQ ID NO: 2-6 or 2 has been mutated to another amino acid residue which is not asparagine, proline or cysteine.

Abstract: The present invention provides a plasmid, method and kit for producing heat labile enterotoxin B-subunit based on a Bacillus subtilis expression system. By comparing with the conventional method in the art, the present invention has the advantages of high safety, good yield, and simplified process and is therefore favorable for the commercialization object of heat labile enterotoxin B-subunit in the application of vaccine adjuvant.

Abstract: A multimeric immunoglobulin-binding protein having improved properties as an affinity ligand for affinity chromatography, and an insoluble support immobilizing such a multimer. The immunoglobulin-binding protein is represented by the formula: (R1)n-(R2)m, or (R2)m-(R1)n. R2 is an immunoglobulin-binding domain including an amino acid residue that covalently bonds to an insoluble support upon immobilization reaction with the insoluble support, and R1 is an immunoglobulin-binding domain without containing an amino acid residue the presence of which in the sequence compared to when it is absent in the sequence reduces the immunoglobulin-binding activity of the support yielded by the immobilization reaction. The immunoglobulin-binding protein satisfies: (1) n is an integer of 5 to 9; (2) m is an integer of 1 or 2; (3) the n (R1) domains may or may not have the same sequence; and (4) the total number of domains (n+m) is 6 to 10.

Abstract: Non-centrifugal methods for generating a solution rich in interleukin-1 receptor antagonist from a tissue comprising cytokine-producing cells. The solution rich in IL-1ra can also include at least one of sTNF-RI, sTNF-RII, IGF-I, EGF, HGF, PDGF-AB, PDGF-BB, VEGF, TGF-?1, and sIL-1 RII.

Abstract: According to the present invention, a mutant rhodocytin lacking platelet aggregation ability is provided. According to the present invention, a pharmaceutical composition including a mutant rhodocytin lacking platelet aggregation ability is provided. According to the present invention, there is provided a method for inhibiting platelet aggregation by a platelet aggregating substance, including administering a pharmaceutical composition including a mutant rhodocytin lacking platelet aggregation ability to a subject in need thereof.

Abstract: The present invention relates to a saxatilin derivative having an increased half life and a use thereof. The saxatilin derivative of the present invention has thrombolytic ability similar to that of saxatilin, which is the mother protein, a remarkably increased protein half life, and efficiently dissolves, for long period of time, blood clots already formed in blood vessels of an animal model with a FeCl3-induced carotid by using the same. Therefore, a composition containing, as an active ingredient, the saxatilin derivative of the present invention does not cause reocclusion after penetration and effectively opens to microvessels, and is thus very useful for treating angiostenosis or occlusive diseases (for example, cerebrovascular diseases, cardiovascular diseases, arteriosclerotic vascular diseases, coronary artery diseases, and peripheral vascular diseases).

Abstract: The present invention relates to the design and development of recombinant protein for the delivery of silencer RNA complex to mediate RNA interference since it represents a novel therapeutic approach to modulate several neurodegenerative disease-related genes across the blood-brain barrier (BBB). To overcome challenges due to this barrier for biologics and other biological complex, the present invention describes a method wherein peptide having sequence GGGGHLNILSTLWKYRC represented by SEQ ID NO. 9 known to target specific gangliosides was linked to a double-stranded RNA binding protein to bind and deliver silencer RNA to the brain parenchyma. The designed fusion protein comprising a double-stranded RNA-binding domain (dsRBD) of human Trans Activation response element (TAR) RNA Binding Protein (TARBP2) and a brain targeting peptide sequence that binds GM1. Conformation-specific binding of TARBP2 domain to silencer RNA results in the formation of homogenous serum-stable complex with GM1 targeting potential.

Abstract: The present invention provides a modified interleukin-7 and a use thereof. The modified IL-7 or an IL-7 fusion protein of the present invention comprising the same can be obtained in high yield, and biologically active in viral infection and cancer models. Therefore, they can be used for the prevention and treatment of various diseases.

Abstract: In one aspect, provided herein is a polypeptide comprising a modified angiopoietin receptor or fragment thereof, wherein the polypeptide binds preferentially to angiopoietin-2 compared to angiopoietin-1. Nucleic acid sequences encoding the polypeptide, as well as pharmaceutical uses of the polypeptide in treating diseases such as cancer and inflammation are also provided.

Abstract: The present invention provides a recombinant strain highly producing fibrinogen which is an animal cell strain coexpressing a fibrinogen and an ?2PI and/or PAI-2, genes encoding A? chain, B? chain and ? chain of fibrinogen, a production method of a recombinant strain highly producing fibrinogen, including introducing gene(s) encoding ?2PI and/or PAI-2 into an animal cell, and coexpressing fibrinogen and ?2PI and/or PAI-2 in the animal cell, and a production method of a recombinant fibrinogen including culturing a recombinant strain highly producing fibrinogen in a medium, and recovering fibrinogen from the obtained culture.

Abstract: The present invention relates to albumin variants with an improved affinity for the neonatal Fc receptor (FcRn) and uses thereof, and in particular to the use of such albumin variants as carriers for immunogens. In some embodiments, the present invention relates to vaccines (e.g., vaccines for mucosal delivery) comprising albumin/immunogen fusion proteins.

Abstract: Molecules and compositions are described for use in the treatment and prevention of pro-inflammatory conditions. HDL-related molecules, including ApoA-I, bovine HDL and HDL mimetics, in particular, are demonstrated to prevent UV-induced cell death and oxidative stress in skin cells and to inhibit tumor growth and development in a variety of cancers. HDL-related molecules can be used as an oral supplement and in other compositions to prevent or treat pro-inflammatory skin conditions and systemic proinflammatory conditions, including Alzheimer's disease and various cancers.

Abstract: The present invention provides novel methods and compositions useful for a fast and efficient chemical conjugation method of making hetero-arm polymers based on thiourea-catechol coupling. This novel conjugation method are useful in a wide variety of applications relating to the modification, ligation, and conjugation of large or small molecules to each other as well as to solid surface, including the making of adhesive materials such as hydrogels.

Abstract: IVIG replacement compounds are derived from recombinant and/or biochemical creation of immunologically active biomimetic(s). These replacement compounds are then screened in vitro to assess each replacement compound's efficiency at modulating immune function. Particular replacement compounds are selected for further in vivo validation and dosage/administration optimization. Finally, the replacement compounds are used to treat a wide range of diseases, including inflammatory and autoimmune diseases.