Abstract: The present application relates to alkoxy-substituted pyridinyl indolsulfonamides. The compounds are negative GPR17 modulators and have utility in the treatment of various GPR17 associated disorders.

Abstract: This invention relates to novel compounds according to Formula (I) which are antagonists of MrgX2, to pharmaceutical compositions containing them, and to their use in therapy for the treatment of MrgX2-mediated diseases and disorders.

Abstract: The present disclosure relates generally to aromatic derivatives that are inhibitors of FGFR4 and are useful in treating FGFR4-associated diseases or conditions. Compositions containing the compounds of the present disclosure are also provided.

Abstract: The present invention relates to an isoindolin-1-on derivative, a method for preparing same, and a pharmaceutical composition comprising same as an effective component for preventing or treating tumors, wherein the isoindolin-1-on derivative exhibits a high inhibitory effect on EGFR mutations, and thus can be beneficially used for the treatment of EGFR-mutated tumors, and the isoindolin-1-on derivative exhibits a significant synergistic effect when co-administered, and thus can be beneficially used in concomitant therapy.

Abstract: The present invention relates to a method for preparing a ?-lactam derivative, wherein a substituted N-quinoline-3-butenamide derivative is used as a substrate to react with a toluene derivative or a heterocyclic derivative at 90-150° C. in the presence of DTBP and a copper salt catalyst, to prepare a ?-lactam derivative. According to the method of the present invention, a variety of ?-lactam derivatives can be obtained with a high yield. The reaction of the present invention has mild reaction conditions, and simple reaction operation and post-treatment process, and is suitable for large-scale production.

Abstract: Invented are compounds of Formula I and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

Abstract: The present invention provides a compound, a salt thereof, or a prodrug thereof as a compound effective for preventing and/or treating fibrosis, the compound being represented by formula (1) (wherein A is an optionally substituted benzene ring; B is optionally substituted aryl or optionally substituted heteroaryl; X is an oxygen atom or a sulfur atom; Y is a nitrogen atom or a carbon atom, of Y is a single or double bond when Y is a carbon atom, or of Y is a single bond when Y is a nitrogen atom; each R1 independently represents lower alkyl, or two R1s may be bound to each other to form a spiro ring or a crosslinked structure, or two R1s may be bound to each other to form a saturated fused heterocycle together with nitrogen and carbon atoms constituting a ring containing Y; p is 0, 1, or 2; or (R1)p is oxo).

Abstract: The invention provides various novel compositions of berberine in combination with pharmacologically active organic acids, and related methods of their use in treating various diseases or disorders. The invention further provides various novel compounds prepared from berberine and pharmacologically active organic acids and prepared from ursodeoxycholic acid and pharmacologically active organic bases, and pharmaceutical compositions thereof, and methods of their preparation and therapeutic use in treating and/or preventing various diseases or disorders.

Abstract: The present invention relates to imidazo-pyridinyl compounds, or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer, in a subject.

Abstract: The invention relates to novel crystalline forms of imiquimod formed with ferulic acid, acetic acid, coumaric acid, citric acid, or tartaric acid, to methods of making these cocrystals, and to compositions containing the cocrystals.

Abstract: Compounds for treating tuberculosis and, particularly, to anti-tubercular compounds that are substituted 7-amino-3-(substituted benzoyl)indolizine-1-carboxylates and their use as anti-tubercular agents.

Abstract: Provided herein are compounds of formula (II): or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, n, p, R1, R2, R3, L1, L2, L3, R4, X1, X2, X3, and X4 are as defined herein. Also provided are methods of preparing compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. Also provided are methods of inhibiting APOL1 and methods of treating an APOL1-mediated disease, disorder, or condition in an individual.

Abstract: This disclosure relates to methods of treatment using compound (1) or analogs thereof, and pharmaceutically acceptable salts thereof. Also disclosed are compounds of formula (10): as defined in the specification, and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions comprising the same. Methods of treatment, such as for cancer, are provided that comprise administering the compounds and their salts to a subject in need of such treatment.

Abstract: The present invention relates to Compounds of Formula I and Ia and pharmaceutically acceptable salts or prodrug thereof, wherein R1, R2, X, A and B are as defined herein. The present invention also relates to compositions comprising at least one compound of Formula I or Ia, and methods of using the compounds of Formula I or Ia for treating or preventing HIV infection in a subject.

Abstract: Novel 5-substituted aminopyrimido[6?,1?:2,3]imidazo[4,5-c][1,6]naphthyridine compounds having the formula I below with all substituents as defined in the instant specification, a method of synthesizing said compounds, a pharmaceutical composition comprising said compounds and a suitable carrier, and a method of using the compounds. The 5-substituted aminopyrimido[6?,1?:2,3]imidazo[4,5-c][1,6]naphthyridine compounds, identified as CK2 inhibitors, are useful as anticancer and/or antitumor agents, and as agents for treating other kinase-associated conditions including inflammation, pain, and certain immunological disorders, and other types of diseases such as diabetes, viral infection, neurodegenerative diseases.

Abstract: The present disclosure provides bifunctional compounds of Formula (I), and pharmaceutically acceptable salts, isotopic forms, isolated stereoisomers, or mixtures of stereoisomers thereof, as IRAK4 degraders via ubiquitin proteasome pathway, and method for treating diseases modulated by IRAK4.

Abstract: The present disclosure provides diacylglycerol kinase modulating compounds, and pharmaceutical compositions thereof, for treating cancer, including solid tumors, and viral infections, such as HIV or hepatitis B virus infection. The compounds can be used alone or in combination with other agents.

Abstract: The present application provides bicyclic amines of Formula (I): and their pharmaceutically acceptable salts thereof, that are inhibitors of cyclin-dependent kinase 2 (CDK2), as well as pharmaceutical compositions thereof, and methods of treating cancer using the same.

Abstract: The present invention provides salts and crystalline forms of Linsitinib (OSI-906; cis-3-[8-amino-1-(2-phenyl-7-quinolinyl)imidazo[1,5-a]pyrazin-3-yl]-1-methyl-cyclobutanol). These forms of Linsitinib provide increased solubility and improved pharmacokinetic profiles for orally administered pharmaceutical formulations. Accordingly, the invention enables improved methods for treating human insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR) mediated conditions.

Abstract: Provided herein are compounds of Formula (I). Methods for the preparation of the compounds of Formula (I) and intermediates useful in the preparation of the compounds of Formula (I) are described herein. The compounds of Formula (I) may be useful as inhibitors of the MYST family of lysine acetyltransferases (KATs) for the treatment of and/or prophylaxis of hyperproliferative diseases, disorders or conditions such as cancer. In particular, the compounds of Formula (I) are useful for the inhibition of KAT6A and KAT6B which are enzymes frequently mutated, overexpressed, amplified and/or translocated in cancer altering their normal expression, activity and function. The use of the compounds of Formula (I) in the manufacture of pharmaceutical compositions or for treating cancers is further described, including for treating cancer in combination with other anti-cancer agents.

Abstract: Compounds for treating tuberculosis and, particularly, to anti-tubercular compounds that are 5-(1H-indol-3-yl)-1,3-substituted-7-thioxo-7,8-dihydropyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione derivatives and their use as anti-tubercular agents. Each compound may have the formula I: or a pharmaceutically acceptable salt or tautomer thereof, wherein: R1 is H or CH3; R2 is H or CH3; and X is O or S.

Abstract: The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis and atopic dermatitis), kits, methods of synthesis, and products-by-process.

Abstract: A new class of ordered functional nanoporous material (OFNMs) with a unique combination of electronic conductivity, gas transport ability, and ion transport properties are provided. The OFNM provided is highly ordered and contains nanometer scale pores lined with nitrogen atoms. The pores have dimensions of from 1.2 nm to 82 nm of longest linear extent across the pore. The functionality within the pore is controlled through selection of groups that extend into the pore. The degree of conjugated aromaticity is readily controlled to adjust the electrical conductivity properties of the resulting structure. By adjusting the groups external to the pore, three-dimensional structures are formed that are organic mimics of zeolites, metal organic frameworks (MOF), or perovskites.

Abstract: Novel pyrazino[1?,2?:1,5]pyrazolo[4,3-b][1,6]naphthyridine, a method of synthesizing said compounds, a pharmaceutical composition comprising said compounds and a suitable carrier, and a method of using the compounds. The pyrazino[1?,2?:1,5]pyrazolo[4,3-b][1,6]naphthyridine compounds, identified as CK2 inhibitors, are useful as anticancer and/or antitumor agents, and as agents for treating other kinase-associated conditions including inflammation, pain, and certain immunological disorders, and other types of diseases such as diabetes, viral infection, neurodegenerative diseases.

Abstract: The benzofuro[3,2-c]-chromen-6-one compounds are antibacterial agents. The emergence of drug-resistant bacteria calls for constant development of new antibacterial agents with the aim of generating medicaments that are potent against drug sensitive and resistant bacteria and are well tolerated. The present compounds are not only new, but have very valuable antimicrobial properties. These compounds showed a broad spectrum of activity against gram-positive and gram-negative bacteria, as well tuberculosis mycobacteria. They also showed potent activity against drug-resistant bacteria, such as MRSA and VRSA. The molecular target of these compounds was identified as DNA Gyrase B. Based on their pharmacological profiles, the present compounds may find important clinical applications for severe infectious diseases and tuberculosis.

Abstract: An intermediate compound is prepared and used for the synthesis of halichondrin B, eribulin or an analog thereof, particularly a structural fragment C27-C35 thereof. The starting materials of the synthetic route are readily available, and the optical purity of the starting materials can be ensured, so that the optical purity of the structural fragment C27-C35 in halichondrin B, eribulin or the analog thereof is ensured. Steps for constructing a chiral center of the structural fragment C27-C35 feature higher diastereoselectivity and yield, in particular preparation methods of compounds of formulae (X), (XI), (XVI) and (XV). By-products of partial reactions can be removed only by recrystallization, which results in easy purification and significant reduce in cost.

Abstract: This invention relates to a novel continuous process for making alkyl 7-amino-5-methyl-[1,2,5]-oxadiazolo¬[3,4-b]pyridine-carboxylate, wherein R is C1-3-alkyl. The process of the invention present invention overcomes disadvantages of processes of the prior art by avoiding the highly energetic intermediates, using readily available and inexpensive starting materials and reagents, and avoiding the isolation of intermediates. The process according to the invention is suitable for use on industrial scale.

Abstract: The present disclosure relates to novel compounds for use in therapeutic treatment of a disease associated with peptidylarginine deiminases (PADs), such as peptidylarginine deiminase type 4 (PAD4). The present disclosure also relates to processes and intermediates for the preparation of such compounds, methods of using such compounds and pharmaceutical compositions comprising the compounds described herein.

Abstract: The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof: which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: The invention provides a new process for producing ruthenium complexes represented by the Formula 1. Invention provides also the use of ruthenium complexes represented by the Formula 1 as precatalysts and/or catalysts in olefin metathesis reactions.

Abstract: Provided are an organometallic compound, an organic light-emitting device including the organometallic compound, and an apparatus including the organic light-emitting device. The organometallic compound may be represented by the formula M11 M12 (L11)n11(L12)n12, wherein M11 and M12 are each independently selected from a Period 1 transition metal, a Period 2 transition metal, and a Period 3 transition metal; L11 is a ligand represented by Formula 1-1 shown below, L12 is selected from a monodentate ligand and a bidentate ligand, n11 is 1, and n12 is selected from 0, 1, 2, 3, and 4.

Abstract: The invention provides a light-stimuli responsive coordination polymer, and preparation method and use thereof. The coordination polymer has a chemical formula of [Zn(tkpvb) (Fb)2]n1, wherein Fb represents p-fluorobenzoate, tkpvb represents 1,2,4,5-tetrakis((E)-2-(4-pyridyl)vinyl)benzene, and n=3000-60000; and crystallographic parameters of: (1) crystal system: monoclinic system; (2) space group: C2/c; (3) a=28.577(3)?, b=7.4084(6) ?, c=22.612(3) ?, ?=126.771(2)°, and V=3834.8(7) ?3; (4) Z=4; and (5) F(000)=1720, R1=0.0440, wR2=0.1042, and GOF=1.047. The method is simple, and has mild reaction conditions, and fast light conversion rate. The means of light-stimuli responsiveness are non-contact and non-damage type, the volume adjustment is highly accurate, and the whole adjustment process does not require any chemical reagents, and is safe and reliable. Photoactuators can complete a variety of behaviors under the irradiation of ultraviolet light having a wavelength of 365 nm.

Abstract: Provided are a novel boron-containing compound and an electrolyte solution additive for a secondary battery including the same. The electrolyte solution for a secondary battery provided in one embodiment includes the novel boron-containing compound, thereby suppressing the decomposition of an electrolyte solution to improve the capacity and the life characteristics of a battery.

Abstract: Solid forms of L-glufosinate materials, including crystalline L-glufosinate ammonium, are described.

Abstract: The invention provides a D-psicose crystal and a preparation method thereof. The method comprises: adding a seed crystal to a D-psicose solution and stirring uniformly, subjecting the solution to crystallization by gradient cooling and constant-temperature crystallization alternately at 50-30° C., stopping the crystallization until the temperature of the solution is 30° C., separating the crystal by centrifugation, washing and drying, to obtain a D-psicose crystal. Rather than evaporative crystallization, organic solvent-assisted crystallization and ultrasonication, controllable crystallization by gradient cooling, constant-temperature crystallization, and other technical means are employed. Thus, the invention has low requirements for equipment, simple process, low energy consumption, and low preparation cost, and thus particularly suitable for large-scale industrial production and processing. The purity of the D-psicose crystal obtained is ?98.

Abstract: The present disclosure relates generally to terpene glycosides, such as certain such compounds extracted from Stevia rebaudiana Bertoni, Rubus suavissimus, or Siraitia grosvenorii. The disclosure also provides for the use of such compounds as food ingredients, flavors, and sweeteners, and related methods. The disclosure also provides ingestible compositions comprising such compounds, as well as processes for extracting such compounds selectively from certain plant sources.

Abstract: Disclosed herein are high Tm RNA nanostructures that can be composed of one or more modules or motifs to build RNA nanostructures with or without layers. The RNA nanostructures can have a core domain and three or more double-stranded arms and formulations thereof to conjugate high copy numbers of therapeutics, pH responsive or enzyme cleavable drug cargo. Also described herein is a design strategy for generation of synthetic RNA oligonucleotides that can self assemble into highly thermostable RNA structures. Also described herein are uses of the RNA nanostructures described herein.

Abstract: The disclosure discloses an ultrasonic-assisted pretreatment method for extraction of multiple steroid hormones in a sediment, including the following steps: (1) lyophilizing the sediment, grinding the sediment, and passing the ground sediment through a 40-60-mesh sieve; (2) placing the sample obtained in step (1) in a container; (3) adding an extractant to the container in step (2), shaking the mixture for 15 s-30 s, centrifuging the mixture to collect an supernatant after ultrasonication, and repeating extraction three times; where the extractants used in the three times of extraction are two of methanol, acetonitrile and acetone; and (4) after mixing the supernatants of the three times of extraction obtained in step (3), concentrating the mixture under a nitrogen flow at 20-30° C., passing the concentrated mixture through a filter, and performing detection. By using the method of the disclosure, the maximum recovery can be up to 100%.

Abstract: A method for preparing peptides is disclosed, the method comprising a step of forming a peptide bond wherein the carboxyl group of a first amino acid or first peptide is activated and an amino group of the first activated amino acid or first peptide is protected by a protecting group having a water-solubility enhancing group and the activated carboxyl group of the first amino acid or first peptide is reacted with an amino group of a second amino acid or second peptide wherein said carboxyl group of the first amino acid or first peptide is activated in the absence of the second amino acid or second peptide. Peptides comprising a protecting group having a water-solubility enhancing group being bound to the amino group and an activated or free carboxyl group are also disclosed.

Abstract: The present disclosure provides recombinant AAV capsid proteins comprising a modification in the amino acid sequence and virus vectors comprising the recombinant AAV capsid proteins. The disclosure also provides methods of administering the virus vectors and vims capsids of the disclosure to a cell or to a subject in vivo.

Abstract: The disclosure provides modified biotin-binding proteins which can be expressed in soluble form in high yield in bacteria. Also provided are fusion proteins comprising the modified biotin-binding protein and an antigen. The disclosure further provides non-hemolytic variants of alpha-hemolysin from S. aureus and fusion protein comprising non-hemolytic variant of alpha-hemolysin and a biotin-binding domains. Immunogenic compositions comprising the proteins are also disclosed and use of such immunogenic compositions for inducing an immune response or for vaccinating a subject are also disclosed.

Abstract: A cooked millet prolamin peptide for inhibiting ?-amylase and ?-glucosidase, an application thereof, and a screening method thereof are disclosed. The sequence of the peptide is selected from SEQ ID NOS: 1-6. The peptide provided in the present disclosure can effectively inhibit the activities of ?-glucosidase and ?-amylase simultaneously and is safe and non-toxic and has no side effects. Therefore, the peptide has a good potential and application prospect as a functional component in food, health products, and hypoglycemic drugs.

Abstract: Mutant M-CSF protein, comprising ?v?3 integrin binding motif and pharmaceutical compositions comprising same, are provided. Further, use of the composition for the treatment and or prevention of diseases associated with increased bone resorption are provided.

Abstract: The present disclosure provides methods for treating or ameliorating a myelin associated disease or a mitochondria associated disease that comprising administering to a subject in need thereof a frataxin replacement therapeutic compound, e.g., a fusion protein comprising frataxin.

Abstract: A compound comprising, in combination: a cell surface binding ligand or internalizing factor, such as an IL-13R?2 binding ligand; at least one effector molecule (e.g., one, two, three or more effector molecules); optionally but preferably, a cytosol localization element covalently coupled between said binding ligand and said at least one effector molecule; and a subcellular compartment localization signal element covalently coupled between said binding ligand and said at least one effector molecule (and preferably with said cytosol localization element between said binding ligand and said subcellular compartment localization signal element). Methods of using such compounds and formulations containing the same are also described.

Abstract: Provided herein are IL-2 muteins and IL-2 mutein Fc-fusion molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also, provided herein are linker peptides that are glycosylated when expressed in mammalian cells.

Abstract: Provided herein are IL-2 muteins, IL-2 mutein Fc-fusion molecules, anti-IL-2 antibodies, and complexes comprising an anti IL-2 antibody bound to an IL-2 cytokine that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also provided herein are linker peptides that are glycosylated when expressed in mammalian cells. Also provided herein are methods of making and using the compositions of the present invention.

Abstract: Myelodysplastic syndrome (MDS) hematopoietic stem and progenitor cells (HSPC) translocate endosomal Toll-Like receptor (TLR)-9 to the plasma membrane, thereby sensitizing these clonal propagating cells to respective ligands in the microenvironment. TLR9 is the cognate receptor for RNA:DNA hybrids (R-loops) and unmethylated CpG oligonucleotides in oxidized mitochondrial DNA, the latter of which is abundant in the bone marrow microenvironment as a result of massive medullary pyroptotic cytolytic cell death. Both ligands are important danger-associated molecular patterns (DAMPs) triggering innate immune activation and chronic inflammation that contributes to MDS pathogenesis. In an effort to neutralize these DAMPs and disrupt this feed-forward inflammatory cascade, a chimeric protein was designed fusing the external epitopes of TLR9 to the Fc domain of human IgG4 to serve as a decoy receptor or ligand trap recognizing extracellular RNA:DNA hybrids (R-loops) and oxidized mitochondrial DNA.

Abstract: The present application provides antibody-TCR chimeric constructs comprising an antibody moiety that specifically binds to a target antigen fused to a TCRM capable of recruiting at least one TCR-associated signaling module. Also provided are methods of making and using these constructs.

Abstract: Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotropin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions and pharmaceutical formulations comprising the polypeptides and polynucleotides of the disclosure and methods of using and producing same are also disclosed.