Abstract: The present invention in one embodiment provides a compound of Formula I: (I), or a pharmaceutically acceptable salt thereof, wherein Y1, Y2 and Y3 are each independently selected from hydrogen and deuterium; R1, R2, and R3 are each methyl and are independently substituted with 0 to 3 deuterium; and R4 is t-butyl and is substituted with 0 to 9 deuterium; provided that if R1, R2 and R3 are each —CH3, and R4 is —C(CH3)3, then at least one of Y1 and Y2 is deuterium.

Abstract: This invention provides quinazoline analogs of Formula I: where A is bonded to at least one of the carbons at the 5, 6, 7 or 8 position of the bicyclic ring, and the ring is substituted by up to two independent R3 groups. The invention also includes methods of using compounds of Formula I as type I receptor tyrosine kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.

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: Co-crystals of Formula I compounds and their pharmaceutical compositions are novel therapeutics for the treatment of diseases, such as human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection and cancer. The co-crystal are more stable to oxidation and aqueous degradation, have a better pharmacokinetic profile and superior biological activity than the corresponding tosylate salt form of Formula I compound.

Abstract: Benzodiazepine dimers having a structure represented by wherein R1 is wherein the variables in formulae (I), (Ia), and (Ib) are as defined in the application. Such dimers are useful as anti-cancer agents, especially when used in an antibody-drug conjugate (ADC).

Abstract: Process to obtain a trifluoromethylating composition which comprises the reaction between a copper (I) source and a base in the presence of a solvent and between the resulting cuprating reagent with fluoroform.

Abstract: The present invention relates to a novel tricyclic benzoxaborole derivative, a preparation method thereof, and use of antibiotics pharmaceutical composition including the same as an active ingredient.

Abstract: The present invention features compounds effective in inhibiting active against Hepatitis C virus (“HCV”) polymerase. The invention also features processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

Abstract: The invention relates to oligonucleotide-oligocation molecules AiBjH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein .Ai is an i-mer oligonucleotide residue, with i=5 to 50, where nucleotide A is an oligomer with naturally or non naturally occurring nucleobases and/or pentafuranosyl groups and/or native phosphodiester bonds, for example selected from the group comprising deoxyribo, ribo, locked (LNA) nucleotides as well as their chemical modifications or substitutions such as phosphorothioate, 2?-fluoro, 2?-O-alkyl, or a marker group such as a fluorescent agent, .Bj is a j-mer organic oligocation moiety, with j=1 to 50, where B is selected from the group comprising .—HPO3—R1—(X—R2n)n1—X—R3—O—, where R1, R2n and R3, identical or different, are lower alkylene, X is NH or NC(NH2)2, n varies from 1 to 5 and n1=2 to 20, .

Abstract: A method for the synthesis of N-(phosphonomethyl)glycine or one of its derivatives selected from the group consisting of its salts, its phosphonate esters, or its phosphonate ester salts, which includes the steps of: a) forming, in the presence an acid catalyst, a reaction mixture having 2,5-diketopiperazine, formaldehyde and a compound including one or more P-0-P anhydride moieties, the moieties having one P atom at the oxidation state (+III) and the other P atom at the oxidation state (+III) or (+V), to form N,N?-bisphosphonomethyl-2,5-diketopiperazine, its mono- to tetra phosphonate esters, the dehydrated forms of N,N?-bisphosphonomethyl-2,5-diketopiperazine and the phosphonate esters of its dehydrated forms; and b) hydrolyzing the N,N?-bisphosphonomethyl-2,5-diketopiperazine, its dehydrated forms or their phosphonate esters to obtain N-(phosphonomethyl)glycine or one of its derivatives selected from the group consisting of its salts, its phosphonate esters and its phosphonate ester salts.

Abstract: Disclosed herein are methods for recovering diphosphonite-containing compounds from mixtures comprising organic mononitriles and organic dinitriles, using multistage countercurrent liquid-liquid extraction. Recovery is enhanced with one or more method steps. In a first step, a portion of the heavy phase from the settling section of the first stage is recycled to the settling section of the first stage. In a second step, a portion of the light phase from the settling section of the first stage is recycled to the mixing section of the first stage. In a third step, the first stage takes place in a mixer-settler, a Lewis base is introduced into the settling section of the first stage, and a complex of Lewis acid and Lewis base is formed in this settling section. In a fourth step, a polyamine is added to the first stage.

Abstract: The present invention relates to the use of silver(I) monophosphine complexes as Active Pharmaceutical Ingredients (API's), including anticancer agents, for the treatment, diagnosis and/or prevention of cancer. The present invention also relates to pharmaceutical compositions containing such complexes and further extends to a method of treating or diagnosing a subject/patient suffering from cancer.

Abstract: The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, esters, or prodrugs thereof: Q-G-A-L-B—Z—W??(I), which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention relates to an efficient process for the separation of diastereomers of 9-[(R)-2-[[(R,S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino]-phenoxyphosphinyl]methoxy]propyl]adenine and to a process for preparing 9-[(R)-2-[[(R)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine and 9-[(R)-2-[[(S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine.

Abstract: Methods for isolating 9-{(R)-2-[((S)—{[(S)-1-(isopropoxycarbonyl)ethyl]amino}phenoxyphosphinyl)methoxy]propyl}adenine (compound 16): a method for preparing in high diastereomeric purity, intermediate compounds 13 and 15: and a method for preparing intermediate compound 12: 9-{(R)-2-[((S)—{[(S)-1-(isopropoxycarbonyl)ethyl]amino}phenoxyphosphinyl)methoxy]propyl}adenine has anti-viral properties.

Abstract: The invention relates to a process for the purification of a contaminated organophosphorus product which comprises at least one organophosphorus compound and, as contaminant, at least one chlorine compound. It is based on the object of indicating a purification method in which the chlorine content of an organophosphorus product which comprises at least one organophosphorus compound and at least one chlorine compound as contaminant, can be reduced from originally 1000 to 100 000 ppm to a total chlorine content between 10 ppm and 10 000 ppm. This is achieved by a process with the steps: a) provision of the contaminated organophosphorus product; b) complete dissolution of the contaminated organophosphorus product in a solvent to give a contaminated solution; c) separation of the contaminated solution by means of a filter and/or by means of a membrane separation unit to give a purified solution; d) removal of the solvent from the purified solution to give a purified organophosphorus product.

Abstract: Compositions of the invention include tunable metal-based thiophene photodynamic compounds useful as therapeutic agents and as in vivo diagnostic agents for treating or preventing diseases that involve hyperproliferating cell etiology including cancer and diseases associated with hyperproliferating cells. The compositions are also useful for treating infectious diseases and for pathogen disinfection.

Abstract: Embodiments of the present disclosure provide for multi-component metal-organic materials (MOMs), systems including the MOM, systems for separating components in a gas, methods of separating polarizable gases from a gas mixture, and the like.

Abstract: Embodiments of the invention are to compounds, methods, and compositions for use in the treatment of viral infections. More specifically embodiments of the invention are 2?,4?-substituted nucleoside compounds useful for the treatment of viral infections, such as HIV, HCV, and HBV infections.

Abstract: Some embodiments of the present invention include nucleoside 5?-monophosphate derivative compounds, their preparation and their uses. In some embodiments, such compounds are useful to treat hepatitis C viral infections.

Abstract: Provided herein are neuroprotective molecules containing a sequence of 25-35 contiguous nucleotides that is at least 80% identical to a contiguous sequence between nucleotide 1 and nucleotide 50 of a mature human tRNA and at least four contiguous guanosine-containing nucleotides, where the sequence of 25-35 contiguous nucleotides contains a D-loop stem structure, the at least four contiguous guanosine-containing nucleotides are located at the 5? end of the neuroprotective molecule, and the neuroprotective molecule contains at least one deoxyribonucleotide. Also provided are methods of inducing or increasing stress granule formation in a cell, decreasing protein translation in a cell, decreasing stress-induced cell death, or treating a neurological disorder associated with neuron death in a subject using at least one of these neuroprotective molecules.

Abstract: A testosterone derivative of formula (I): where n is an integer in a range of from 1 to 10, and Y represents an activated or ready-to-be-activated group allowing formation of an amide bond with a primary amine of a molecule. Conjugates including the testosterone derivatives and a marker, methods for determining the concentration of testosterone in a biological sample, and methods for preparing the testosterone derivatives are also provided.

Abstract: The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.

Abstract: Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described.

Abstract: The present invention relates to a new process for the synthesis of compounds of formula (I) (wherein the meaning of R is dimethylamino or acetyl group) using the compound of formula (II) (wherein the meaning of R is dimethylamino or 2-methyl-1,3-dioxolan-2-yl group) as starting material, as well as to the intermediate of the process.

Abstract: The present invention relates to a novel process for the synthesis of abiraterone and in particular abiraterone acetate, a compound of formula (I) reported below: having pharmacological activity suitable for slowing down the progression of advanced stage prostate cancer. The process is characterized by the fact that the intermediate triflation step is carried out on prasterone (DHEA) or its 3-acetate using Ar—N(OTf)2 as the triflation reagent, but where Ar is not phenyl, and by the fact that the base used in this step is an alkali metal alcoholate.

Abstract: In one aspect, affinity tags for recombinant protein purification are described herein which, in some embodiments, can mitigate or overcome disadvantages of prior affinity tag systems. In some embodiments, for example, affinity tags described herein permit efficient elution of desired recombinant proteins with simplified solution systems, such as alkali metal salt solutions. An affinity tag described herein comprises an amino acid sequence including a repeating amino acid unit of BXXXBXX, wherein B is an amino acid selected from the group consisting of histidine, lysine and arginine and X is an amino acid selected from the group consisting of amino acids other than histidine, lysine and arginine.

Abstract: The author attempted and succeeded in separating and purifying the cysteine protease inhibitors from new gingers. The root and stem of new gingers were extracted with neutral buffer which subsequently underwent heat treatment at 80° C. for 10 minutes. After centrifugal separation, the supernatant was separated with acetone. The fractions that precipitated at an acetone concentration of 55-77% were injected into a chromatographic column of DEAE-cellulose and Sephadex G-75 gel for purification. The results demonstrated that there were two cysteine protease inhibitors with a molecular weight of 11,000-11,800 and 15,500-16,000, respectively, which strongly inhibit papain. The two cysteine protease inhibitors do not have high heat stability.

Abstract: The present disclosure is directed to a novel class of toll-like receptor 2-agonistic (TLR2) lipopeptide compounds having specific structures, and synthetic methods of making the compounds. These compounds provide high potency of agonistic activities with human, other than murine, TLR2, and are useful as vaccine adjuvants. Vaccines are perhaps one of the most successful medical interventions against infectious disease.

Abstract: This invention relates to a method for treating or preventing a disease by raising an innate immune response in a subject, the method comprising administering to the subject an effective amount of a composition comprising a TLR2 moiety in solution, wherein the TLR2 moiety comprises a TLR2 agonist and wherein the disease is not treated or prevented by a humoral or cellular immune response directed against the TLR2 moiety.

Abstract: A method is provided for inhibiting proliferation of a high LIX1L-expressing tumor cell, in which the expression or function of a LIX1L gene with respect to a tumor cell highly expressing the LIX1L gene is inhibited.

Abstract: The invention features echinocandin class compounds. The compounds can be useful for the treatment of fungal infections.

Abstract: Disclosed is an oligopeptidic compound capable of interacting with proliferating cell nuclear antigen (PCNA), wherein the compound comprises a PCNA interacting motif which is: (SEQ?ID?NO.?28) [K/R]-[F/Y/W]-[L/I/V/A/M]-[L/I/V/A/M]-[K/R]; wherein the oligopeptidic compound has 9-70 subunits and comprises at least one signal sequence, wherein the signal sequence is a nuclear localization signal sequence and/or a cell penetrating signal sequence and wherein in said compound a PCNA interacting motif is N-terminal to a signal sequence. Also disclosed are methods of treatment of a disorder or condition where it is desirable to inhibit the growth of cells, or a method of treatment which involves cytostatic therapy, or a method of treatment of inflammation said method comprising administering the oligopeptidic compound to a subject in need thereof.

Abstract: A polypeptide with a predominantly hydrophobic sequence long enough to span a membrane lipid bilayer as a transmembrane helix (TM) and comprising one or more dissociable groups inserts across a membrane spontaneously in a pH-dependant fashion placing one terminus inside cell. The polypeptide conjugated with various functional moieties delivers and accumulates them at cell membrane with low extracellular pH. The functional moiety conjugated with polypeptide terminus placed inside cell are translocated through the cell membrane in cytosol. The peptide and its variants or non-peptide analogs can be used to deliver therapeutic, prophylactic, diagnostic, imaging, gene regulation, cell regulation, or immunologic agents to or inside of cells in vitro or in vivo in tissue at low extracellular pH.

Abstract: Herpes Simplex Virus (HSV) antigens that elicit an HSV-specific immune response and can be used to treat or prevent HSV infection are provided. Nucleic acid sequences, polypeptides, vectors, and compositions, as well as methods to induce an immune response against HSV, treat or prevent HSV disease, induce a T cell response against HSV, and induce an antibody response against HSV also are provided.

Abstract: The invention relates to chimeric vaccine antigens against hepatitis C virus (HCV) comprising selected regions of different antigens of said virus, which are placed in a pre-determined order inside the polypeptide. In addition, said chimeric antigens can include artificially formed specific epitopes for auxiliary T helper lymphocytes. The chimeric antigens and the resulting vaccine compositions are suitable for use in medicine and the pharmaceutical industry, as well as being suitable for prophylactic and/or therapeutic use against HCV. The vaccine compositions of the invention generate a powerful, broad-spectrum immune response against different antigens of the virus, with a minimum number of components.

Abstract: A vaccine composition comprising a fusion protein for inducing enhanced pathogen antigen-specific T cell responses is disclosed. The fusion protein comprises: (a) an antigen-presenting cell (APC)-binding domain or a CD91 receptor-binding domain, located at the N-terminus of the fusion protein; (b) a translocation peptide of 34-112 amino acid residues in length, comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 4, 2, 3, or 6, located at the C-terminus of the APC-binding domain or the CD91 receptor-binding domain; and (c) an antigen of a pathogen, located at the C-terminus of the translocation peptide; (d) a nuclear export signal, comprising the amino acid sequence of SEQ ID NO: 13; and (e) an endoplasmic reticulum retention sequence, located at the C-terminus of the fusion protein.

Abstract: A fusion protein for use as an immunogen enhancer for enhancing antigen-specific T cell responses is disclosed. The fusion protein comprises: (a) an antigen-presenting cell (APC)-binding domain or a CD91 receptor-binding domain; (b) a protein transduction domain; and (c) an antigen of a pathogen, wherein the APC-binding domain or the CD91 receptor-binding domain is located at the N-terminus of the fusion protein, and the antigen of the pathogen is located at the C-terminus of the protein transduction domain. The protein transduction domain is selected from the group consisting of: (i) a fusion polypeptide, comprising a T cell sensitizing signal-transducing peptide, a linker, and a translocation peptide; (ii) a T cell-sensitizing signal-transducing peptide; and (iii) a translocation peptide of 34-112 amino acid residues in length.

Abstract: The present invention relates to rearranged molecules of (a) a specific TT virus sequence and (b) a nucleotide sequence encoding a polypeptide showing homology to mammalian proteins associated with cancer and autoimmune diseases that are capable of replicating autonomously for use in diagnosis, prevention and treatment of diseases like cancer and autoimmunity.

Abstract: The present invention discloses polypeptides with antibacterial properties and use said polypeptides and/or polynucleotides encoding said polypeptides in the preparation of medicament for the treatment of infectious diseases. The inventors also provide vectors encoding and adapted for expression of the polypeptides and polynucleotides of the invention. The vectors may be used in the preparation of a medicament for the treatment of bacterial infections. Further, the vector of the invention may be used to reduce the load of bacteria in food and/or feed.

Abstract: The present invention relates to chimeric GH61 polypeptides having cellulolytic enhancing activity. The present invention also relates to polynucleotides encoding the chimeric GH61 polypeptides; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the chimeric GH61 polypeptides.

Abstract: Transcription factor polynucleotides and polypeptides incorporated into nucleic acid constructs, including expression vectors, have been introduced into plants and were ectopically expressed. Transgenic plants transformed with many of these constructs have been shown to have increased tolerance to an abiotic stress (in some cases, to more than one abiotic stress), increased growth, and/or increased biomass. The abiotic stress may include, for example, salt, hyperosmotic stress, water deficit, heat, cold, drought, and/or low nutrient conditions.

Abstract: The present invention provides a dendritic cell modulatory protein which modulates, and preferably inhibits, the differentiation and/or maturation of mammalian dendritic cells. The invention also provides proteins comprising conserved motifs found in such proteins as well as pharmaceutical compositions comprising the dendritic cell modulatory protein and homologs and active fragments thereof, antibodies thereto and methods of treatment which utilize such proteins, homologs, fragments and antibodies.

Abstract: Complexes containing one or more modular recognition domains (MRDs) and MRDs attached to scaffolds including antibodies are described. The manufacture of these complexes are the use of these complexes to treat and diagnose diseases and disorders are also described.

Abstract: Embodiments of the invention provide to fibulin 3 (also referred to as EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1)) polypeptide variants, and nucleotide sequences that code for them, characterized by having one or more activities of inhibiting cancer growth, inhibiting cancer cell invasion, and inhibiting cancer recurrence.

Abstract: The present disclosure describes recombinant human chorionic gonadotropin (hCG) and methods for the production thereof. The recombinant hCG can include ?2,3, ?2,6, and, optionally, ?2,8 sialylation. The recombinant hCG can be produced in a human cell line such as a PER.C6® cell line.

Abstract: Methods and compositions are used to identify and characterize new channelrhodopsins derived from algae and several of which are red-shifted. The rhodopsin domain of these red-shifted channelrhodopsins can be cloned and expressed in mammalian systems and used in optogenetic applications and as therapeutic agents. Also provided are methods and compositions for use in red-shifting the absorbance maxima of channelrhodopsins in order to improve their utility for use in vivo.

Abstract: Disclosed are methods of making collagen 7, or functional fragments thereof, as well as collagen 7, and functional fragments thereof produced by such methods, nucleic acids encoding collagen 7, and functional fragments thereof, as well as vectors and host cells comprising such nucleic acids.

Abstract: Use of a nutritional supplement for increasing the bacterial mass in the rumen of a ruminant. The nutritional supplement includes proteins with a degree of hydrolysis above 28% and has more than 23 mg ?-amino nitrogen per gram of protein. The hydrolyzed proteins are preferably hemoglobin.

Abstract: The present disclosure relates to the antibody engineering field and, more particularly, to a process for the screening of antibodies and/or the modulation of the agonistic/antagonistic activity of antibodies. More particularly, the disclosure concerns a process of improving the antagonistic activity of a monoclonal antibody directed against a specific target molecule, or a divalent functional fragment or derivative thereof, the antibody being capable of inhibiting one or more of the biological activities of the target molecule, wherein the process comprises a stage of reconfiguration of the hinge region consisting of a modification of the amino acid sequence of the hinge region by the deletion, the addition or the substitution of at least one amino acid. The disclosure also relates to polypeptides useful for such a modulation method and the obtained antibodies.