Abstract: The present invention provides novel CDK7 inhibitors and pharmaceutical compositions thereof: or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), LRKK2, EphA2, polo kinase 1, 2, 3, or 4, Ack1, Ack2, Abl, DCAMKL1, ABL1, Abl mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.

Abstract: The present invention provides a heterocyclic compound having an RIP1 kinase inhibitory action, which is useful for the prophylaxis or treatment of Gaucher's disease, Niemann-Pick disease, inflammatory bowel disease, multiple sclerosis, chronic kidney disease, acute kidney injury, acute hepatic failure, autoimmune hepatitis, hepatitis B, hepatitis C, alcohol steatohepatitis, non-alcohol steatohepatitis and the like. The present invention relates to a compound represented by the following formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

Abstract: The invention relates to novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

Abstract: The use of zinc ketoiminate complexes in the production of polyurethanes is described, wherein the zinc ketoiminate complexes are obtainable by reacting a zinc compound with certain ketimines.

Abstract: Provided herein are lanthanide complexes that exhibit specific subcellular localization to primary cilium. The lanthanide complexes provided herein are useful for imaging, tagging, and pull down of binding targets located in primary cilium.

Abstract: A pure composition comprises a monoalkyltin trialkoxide compound represented by the chemical formula RSn(OR?)3 or a monoalkyl tin triamide compound represented by the chemical formula RSn(NR?2)3 and no more than 4 mole % dialkyltin compounds relative to the total tin amount, where R is a hydrocarbyl group with 1-31 carbon atoms, and wherein R? is a hydrocarbyl group with 1-10 carbon atoms. Methods are described for the formation of the pure compositions. A solid composition comprises a monoalkyl triamido tin compound represented by the chemical formula RSn—(NR?COR?)3, where R is a hydrocarbyl group with 1-31 carbon atoms, and where R? and R? are independently a hydrocarbyl group with 1-10 carbon atoms. The compositions are suitable for the formation of resist compositions suitable for EUV patterning in which the compositions have a high EUV absorption.

Abstract: A polycyclic compound and an organic electroluminescence device, the polycyclic compound being represented by Formula 1:

Abstract: Acyl germanium compound according to general formula [RmAr—(C?O)—]4—Ge and process for the preparation thereof. The compound is suitable as initiator for radical polymerization.

Abstract: A process for the purification of L-?-glycerophosphorylcholine is described, wherein L-?-glycerophosphorylcholine is crystallized from DMSO or from a mixture of DMSO with at least another solvent, preferably selected from water, alcohol, halogenated solvents, ethers, esters and/or amides. Such a process allows to obtain L-?-glycerophosphorylcholine having a purity greater than 99.5%, preferably greater than 99.7%, even more preferably greater than or equal to 99.9%. A method for determining the purity of L-?-glycerophosphorylcholine is also described, comprising the elution of L-?-glycerophosphorylcholine through an HPLC column having an amino stationary phase, and subsequent detection of L-?-glycerophosphorylcholine itself, and any impurity thereof, by means of an Evaporative Light Scattering Detector type.

Abstract: A method of preparing a solid-supported phospholipid bilayer is provided. The method includes a) a first step of providing a solution comprising a bicellar mixture of a long-chain phospholipid and a short-chain phospholipid; b) at least one second step of decreasing the temperature of the solution to below 0° C., increasing the temperature to above room temperature and causing the solution to be blended; and c) a third step of depositing the solution obtained after the second step on a surface of a support, wherein the concentration of the long-chain phospholipid in the solution is at most 0.1 mg/mL, for obtaining a solid-supported phospholipid bilayer. A solid-supported phospholipid layer obtained by the method as defined above is also provided.

Abstract: A 1,3-dipolar compound bearing at least a phosphorus-containing group and a dipole containing a nitrogen atom is provided. A method for grafting the 1,3-dipolar compound on an unsaturated polymer, a diene polymer comprising, along the polymer chain, at least one pendant phosphorus-containing group, and a rubber composition based on a diene elastomer and the 1,3-dipolar compound optionally pre-grafted on the diene elastomer are also provided. The 1,3-dipolar compound allows access to rubber compositions reinforced with an inorganic filler that have a compromise of improved properties, namely hysteresis, stiffness in the cured state and reinforcement.

Abstract: The invention relates to prodrug compounds of formula I: wherein R2, R3, R5, R7 and X are as defined herein. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders, including pain. The compounds of formula I possess advantageous solubility and physicochemical properties.

Abstract: Disclosed is a pH-responsive fluorescent compound, represented by the general formula, which is a novel pH-responsive fluorescent compound capable of being specifically localized in mitochondria within cells, which exhibits strong fluorescence under weakly acidic pH environments in lysosomes, and which is not readily subject to interference from autofluorescence and background fluorescence due to other fluorescent substances within cells. Also disclosed are a composition for detecting mitophagy using the pH-responsive fluorescent compound, and a method for detecting mitophagy within cells. In the general formula, L represents a linker, X represents a pharmaceutically acceptable anion, and Y represents a reactive group that may react with a functional group on a mitochondrial protein to form a covalent bond.

Abstract: A platinum organosiloxane complex is prepared by a process including 1) combining A) a platinous halide and B) a ketone, and thereafter 2) adding C) a polyorganosiloxane having, per molecule, 2 to 4 silicon bonded terminally unsaturated hydrocarbon groups having from 2 to 6 carbon. The platinum organosiloxane complex prepared by the process is useful as a hydrosilylation catalyst.

Abstract: The present disclosure related to a method of producing a color stable, light colored lignin. The method includes: reacting a lignin composition with a hypochlorite composition having about 5% to about 70% available chlorine; and reacting the hypochlorite treated lignin with hydrogen peroxide at a concentration of about 5% to about 50% to produce the light colored lignin, wherein the lignin composition includes at least one of sulfonated lignin, lignosulfonate, or both.

Abstract: An object of the present invention is to provide glycoamino acid as an amino acid precursor with improved properties (particularly water-solubility, stability in water, bitter taste etc.). The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a salt thereof.

Abstract: The present invention relates to a solid form of a compound of Formula (I), a method for preparing the solid form, a pharmaceutical composition comprising the solid form, and the use of the solid form in the treatment of a disease involving abnormal cell proliferation or a viral infectious disease.

Abstract: Enantiomers of 1?,6?-isoneplanocin, including derivatives of the enantiomers of 1?,6?-isoneplanocin, are disclosed along with novel synthetic methods. In particular, a substituted cyclopentane epoxide is synthesized into the enantiomers of 1?,6?-isoneplanocin. Enantiomers of carbocyclic nucleoside analogs of 3-deazaneplanocin to provide D- and L-like 1?,6?-iso-3-deazaneplanocin are also disclosed. The small molecule chemotherapeutic compounds beneficially provide DNA and RNA antiviral activity, demonstrating activity towards, for example, human cytomegalovirus, measles, Ebola, norovirus, dengue, vaccinia and HBV. Compounds exhibiting reduced S-adenosylhomocysteine hydrolase inhibitory effects are disclosed and provide improved toxicity profiles in comparison to neplanocin. The invention provides improved prophylactic and/or therapeutic antiviral efficacy.

Abstract: A crystal of free acid of 3?,5?-cyclic diguanylic acid containing no metal salt with cobalt, magnesium or the like is provided. A method is sought for obtaining said crystal in a large amount and with ease. By a manufacturing method comprising a step of adding acid to an aqueous solution of 3?,5?-cyclic diguanylic acid so as to lower pH to 1 to 3, crystals of 3?,5?-cyclic diguanylic acid can be obtained in a large amount with ease. Said crystals are free acid crystals which do not contain a metal salt with cobalt, magnesium or the like.

Abstract: Disclosed herein are novel cytotoxic peptides of formula (I) as described herein: and the use of such peptides in making immunoconjugates (i.e Antibody Drug Conjugates) Also described herein are immunoconjugates (i.e Antibody Drug Conjugates) comprising such novel cytotoxic peptide linked to an antigen binding moiety, such as an antibody; where such immunoconjugates are useful for treating cell proliferative disorders. The invention further provides pharmaceutical compositions comprising these immunoconjugates, compositions comprising the immunoconjugates with a therapeutic co-agent, and methods to use these immunoconjugates and compositions for treating cell proliferation disorders.

Abstract: The present invention relates to compounds and compositions for use in enhancing flavor and umami taste of food products. Particularly, the present invention relates to compounds of the general formula (I) and compositions comprising them.

Abstract: The present disclosure relates to novel compounds and pharmaceutical compositions thereof which are useful as inhibitors of proteasomes. The compounds provided herein have improved proteasome potency and selectivity, and increased aqueous solubility, and are useful in treating various conditions or diseases associated with proteasomes.

Abstract: The present invention relates to peptidomimetics of the formula (I) or (I)c wherein L1, L2, L3, R1, R2, R3, R4, R5, R6, n, m, Q, X, Z1 and Z2 are defined as mentioned in the description and to salts and solvates of each of these compounds and to processes for the preparation thereof, compositions containing them and the uses of such compounds. It has been found that the compounds have a high microbicide activity and are suited to combat resistant bacteria, such as meticillin-resistant Staphylococcus aureus (MRSA) strains, at very low concentrations.

Abstract: The invention provides PCSK9 inhibitors, compositions comprising the PCSK9 inhibitors, and methods of identifying and using the PCSK9 inhibitors.

Abstract: The invention relates to a peptide comprising (i) a main chain comprising at least one L-3,4-dihydroxyphenylalanine (DOPA), (ii) at least one integrin binding peptide, and (iii) at least one heparin binding peptide. The invention further relates to a coating for metal surfaces comprising the peptide according to the invention and a coated metal surface which promotes osseointegration that can be obtained by reacting the peptide according to the invention with a metal surface.

Abstract: The template-fixed ?-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, have CXCR4 antagonizing properties and can be used for where cancer is mediated or resulting from CXCR4 receptor activity.

Abstract: Presented herein are cyclic peptides that specifically bind to a cell surface molecule, thereby allowing cell/tissue-specific targeting. The cyclic peptides can be attached to an agent, for example, a polypeptide such as an antibody, e.g., a cell-penetrating antibody. Cyclic peptide-containing cell/tissue-specific cell-penetrating antibodies described herein are capable of targeted delivery in a cell type-specific or tissue-specific (i.e., cell/tissue-specific) manner. The cell/tissue-specific cell-penetrating antibodies described herein can be used as an effective anticancer agent for cancer that overexpresses a cell membrane protein that specifically binds to the fused cyclic peptides.

Abstract: Photosynthetic microorganisms with broadened light absorption capability and increased photosynthetic activity are described. Broadened light absorption is achieved by modifying the microorganism to utilize non-native bilins. Increased photosynthetic activity results from the broadened light absorption and can also result from a decrease in self-shading. The microorganisms include Cyanobacteria, including modified Cyanobacteria.

Abstract: The invention comprises a photoautotrophic organism, generally having simpler nutritional requirements than heterotrophic organisms, utilized as a chassis for the heterologous expression and function of enzymes, or derivatives of said enzymes, that show activity toward the degradation/detoxification of toxins known to be associated with and specific to harmful algal blooms. As an example, a cyanobacterial strain (Synechocystis sp. PCC 6803) modified to express Sphingomonas sp. USTB-05 MlrA enzyme functionality, showing the capability of degrading microcystins (results shown here) and nodularins, is presented. Under modelled natural conditions, results indicate that heterologous enzymatic activity against microcystin-LR is more stable over time when utilizing a photoautotrophic chassis in comparison to use of a heterotrophic bacterial strain. In addition, both the viability and cell density of the photoautotrophic host is maintained for a significantly longer period of time, compared to a heterotrophic host.

Abstract: Peptide inhibitors of the interleukin-23 receptor, and related compositions and methods of using these peptide inhibitors to treat or prevent a variety of diseases and disorders, including inflammatory bowel diseases, are described.

Abstract: The present disclosure relates to novel, specific-binding therapeutic and/or diagnostic proteins directed against Glypican-3 (GPC3), which proteins preferably are muteins of a lipocalin protein, more preferably of lipocalin 2 (Lcn2 or NGAL). Present disclosure also relates to nucleic acid molecules encoding such proteins and to methods for generation and use of such proteins and nucleic acid molecules. Accordingly, present disclosure also is directed to pharmaceutical and/or diagnostic compositions comprising such lipocalin proteins, including uses of these proteins.

Abstract: An improved cell-permeable (iCP)-SOCS3 recombinant protein and uses thereof. The iCP-SOCS3 recombinant protein may be used as protein-based anti-angiogenic agent by utilizing the platform technology for macromolecule intracellular transduction. The iCP-SOCS3 recombinant protein includes a SOCS3 protein and at least one advanced macromolecule transduction domain (aMTD)(s). The aMTD(s) is composed of 9-13 amino acid residues and has the following features (a)-(c): (a) having 3 or more amino acid residues independently selected from the group consisting of Ala, Val, Ile, Leu, and Pro; (b) having Proline as an amino acid residue corresponding to any one or more of positions 5, 7 and 8, and position 12 of its amino acid sequence; and (c) having an instability index of 40-60, an aliphatic index of 180-220, and a grand average of hydropathy (GRAVY) score of 2.1-2.6, according to Protparam computational formula.

Abstract: The present invention relates to a modified cytokine of the TNF superfamily, with reduced activity to its receptor, wherein said modified cytokine is specifically delivered to target cells. Preferably, said modified cytokine is a single chain variant of the TNF superfamily, even more preferably, one or more of the chains can-y one or more mutations, resulting in a low affinity to the receptor, wherein said mutant cytokine is specifically delivered to target cells. The targeting is realized by fusion of the modified cytokine of the TNF superfamily to a targeting moiety, preferably an antibody or antibody-like molecule. The invention relates further to the use of such targeted modified cytokine of the TNF superfamily to treat diseases.

Abstract: Disclosed herein are fusion proteins comprising: (a) a first polypeptide comprising Interleukin-2 (IL2); and (b) a second polypeptide, fused in frame to the first polypeptide, wherein the second polypeptide comprises an extracellular domain of Interleukin-2 Receptor alpha (IL2R?), wherein IL2 or IL2R? comprises at least one fewer glycosylation site compared to native IL2 or native IL2R?. Methods of production and methods of therapeutic use of the fusion proteins are also disclosed.

Abstract: The present invention relates to a monoclonal antibody platform designed to be coupled to therapeutic peptides to increase the half-life of the therapeutic peptide in a subject. The invention also relates to pharmaceutical compositions and methods for use thereof.

Abstract: The present invention relates to a cancer treatment composition for inhibiting angiogenesis, and a preparation method therefor. An angiogenesis inhibitor according to the present invention is a cancer treatment composition comprising a fusion protein comprising a vascular endothelial growth factor-binding domain of vascular endothelial growth factor receptor 1 (VEGFR1) and a b1 domain of neuropilin-1 (NRP1). The novel fusion protein is an angiogenesis inhibitor for blocking the binding of VEGF to a receptor in the cell membrane, and has an effect of inhibiting the proliferation of cancer cells and the growth and metastasis of cancer. In addition, the fusion protein can be used as an anti-cancer agent and exhibits an effective anti-cancer effect at a lower dose than that of a conventional angiogenesis inhibitor.

Abstract: Provided herein are polypeptides comprising a modified fibronectin type III (Fn3) domain, wherein the amino acid corresponding to residue 58 of SEQ ID NO: 1 is mutated, and wherein the solubility is enhanced relative to the solubility of a Fn3 domain in which the amino acid corresponding to residue 58 of SEQ ID NO: 1 is not mutated. Also provided are libraries comprising a plurality of the polypeptides and a method for identifying a polypeptide that binds to a target.

Abstract: Certain embodiments of the invention provide epithelial cell adhesion molecule (EpCAM) binding polypeptides, as well as conjugates and CSANs comprising such polypeptides. Additionally, certain embodiments of the invention also provide methods of using such polypeptides and compounds for molecular imaging and molecularly targeted therapies.

Abstract: Methods for purifying multispecific antibodies on interest (MAIs) that co-engage at least two different antigens or epitopes (also referred to targets, used interchangeably throughout), from compositions comprising the MAI and parental homodimeric antibody species are provided, as well as reagents which may be used to practice such methods.

Abstract: The present disclosure provides antibodies and antigen-binding fragments thereof that bind specifically to a coronavirus spike protein and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., coronavirus infections).

Abstract: The present invention relates to methods for treating or ameliorating hypercytokinemia and viral infections associated with hypercytokinemia using norketotifen or a pharmaceutically acceptable salt thereof, optionally in combination with an antiviral agent.

Abstract: The present disclosure is directed to antibodies binding to and neutralizing Chikungunya virus (CHIKV) and methods for use thereof.

Abstract: The invention is directed to compositions and methods for stimulating, enhancing or modulating the immune system of a patient before or after infection by a pathogen, and in particular multidrug resistant (MDR) MTB and extremely drug resistant (XDR) MTB. Compositions of the invention contain non-naturally occurring antigens that generate an effective cellular and/or humoral immune response to MTB and/or antibodies that are specifically reactive to MTB antigens. The greater activity of the immune system generated by a vaccine of the invention increases generation of memory T cells that provide for a greater and/or extended response to an MTB infection. Responses involve an increased generation of antibodies that enhance immunity against MTB infection and promote an enhanced phagocytic response.

Abstract: The present invention relates to an oligopeptide and conjugates thereof. The present invention also relates to the use of these oligopeptide conjugates for treating or diagnosing disorders mediated by amyloid ? deposits. Finally, the present invention also relates to a coupling method for obtaining oligopeptide coupled with a substance of interest (functional conjugates).

Abstract: The present invention relates to a neutralising antibody which is capable of binding to neurotensin with high affinity. The antibody of the present invention neutralises the activity of neurotensin, in particular the oncogenic activities of neurotensin. In particular, the present invention relates to a neutralising antibody which binds to the human neurotensin long fragment, and having a heavy chain variable region which comprises a H-CDR1 region having at least 90% of identity with SEQ ID NO:2, a H-CDR2 region having at least 90% of identify with SEQ ID NO:3 and a H-CDR3 region having at least 90% of identity with SEQ ID NO:4; and a light chain variable region comprising a L-CDR1 region having at least 90% of identity with SEQ ID NO:6, a L-CDR2 having at least 90% of identity with SEQ ID NO:7 and a L-CDR3 region having at least 90% of identity with SEQ ID NO:8. The present invention also provides the use of such antibodies in the treatment of cancer.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat thrombosis in diseases associated with abnormal blood coagulation or fibrinolysis. In preferred embodiments these patients will comprise those exhibiting elevated D-dimer or other cogulation cascade related proteins and optionally will further exhibit elevated C reactive protein prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, et al.

Abstract: The present invention relates to antibody molecules and functional fragments thereof, capable of binding to tumor necrosis factor alpha (TNF?), to processes for their production, and to their therapeutic uses.

Abstract: The present disclosure relates to compositions, for treating interleukin 5 (IL-5) mediated diseases, and related methods.

Abstract: The present disclosure provides proteins comprising antigen binding sites of antibodies that bind to interleukin-21 (IL-21) and uses thereof, e.g., in therapy.