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

Abstract: The present invention relates to substituted tetrahydropyridothienopyrimidine compounds of general formula (I) as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyperproliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

Abstract: p38 and JNK mitogen activated protein (MAP) kinase al losteric inhibitors are useful for treatment and/or prophylaxis of degenerative diseases of the nervous system. Compounds are used in a method for treatment and/or prophylaxis of the diseases and for use in therapy in general. The compounds bind to the region composed of amino acids at positions 170-199 of Mitogen-activated protein kinase 14 (Uniprot accession nr Q16539 or SEQ ID No 1) and/or Mitogen-activated protein kinase 11 (Uniprot accession nr Q15759 or SEQ ID No 2), SEQ ID NO.1 and SEQ ID NO.2 being the amino acid sequences of MAPK14 (?38?) and MAPK11 (?38?), respectively. The specific region composed of amino acids at positions 170-199 is herein disclosed as SEQ ID HO.4 for Mitogen-activated protein kinase 14 and SEQ ID NO.5 for Mitogen-activated protein kinase 11 and are believed to be new inhibitory binding sites.

Abstract: The invention features compounds of Formula (I), Formula (I)-A and Formula (I)-B as disclosed herein, as well as methods of synthesis, therapy, diagnostics, and assays.

Abstract: Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R2, R2a R3 and R3a are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

Abstract: The present invention relates to novel fused Imidazobenzothiazole derivatives, their pharmaceutically acceptable salts, and their isomers, steroisomers, atropisomers, conformers, tautomers, polymorphs, hydrates, solvates and N-oxide. The present invention also encompasses pharmaceutically acceptable compositions of said compounds and process for preparing novel compounds. The invention further relates to the use of the above-mentioned compounds for the preparation of medicament for use as pharmaceuticals.

Abstract: The present invention provides the following compound having anti-HIV activity of formula: wherein, A1 is C, CR1A or N; A2 is C, CR2A, or N; A3 is CR3A, CR3AR3B, N, NR3C, O, S, SO, or SO2; A4 is CR4A, CR4AR4B, N, NR4C, O, S, SO, or SO2; A5 is C, CR5A, or N; T1 ring is substituted or unsubstituted monocyclic carbocycle or substituted or unsubstituted monocyclic heterocycle; R1 is halogen, cyano, nitro or —X1—R11; R2 is substituted or unsubstituted alkyl and the like; n is 1 or 2; R3 is hydrogen, substituted or unsubstituted aromatic carbocyclyl; R4 is hydrogen or a carboxy protecting group; the other symbols are as specified in the description.

Abstract: A method of treating a patient suffering from lymphoma comprising administering to said patient a therapeutically active amount of a compound formula I, or pharmaceutically acceptable salt or solvate thereof, wherein: the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3; R2 and R3 are independently selected from —H, ?O, ?CH2, —CN, —R, OR, halo, ?CH—R, O—SO2—R, CO2R and COR; R6, R7 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo; where R and R? are independently selected from optionally substituted C1-2alkyl, C3-20heterocyclyl and C5-20aryl groups; R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, NH, and/or aromatic rings, e.g. benzene or pyridine, and each X is independently selected from O, S, or NH; R2?, R3?, R6?, R7? and R9? are all independently selected from the same lists as previously defined for R2, R3, R6, R7 and R9 respectively.

Abstract: A compound of Formula II or a pharmaceutically acceptable salt thereof, are capable of monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula II, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula II or a pharmaceutically acceptable salt thereof.

Abstract: Metal-organic frameworks, in particular hybrid zeolitic imidazolate frameworks (ZIFs), devices having hybrid ZIFs, and methods for preparing hybrid ZIFs are disclosed herein. In some embodiments, the method includes preparing a first solution comprising a first imidazolate and a second imidazolate, preparing a second solution comprising a metal ion, and combining the first solution and the second solution to form the hybrid ZIF.

Abstract: The present invention relates to a new generation of PDT agents based on porphyrin-lanthanide complexes with specific functional groups which can specifically localize on particular tumors, and their PDT processes can be monitored via NIR emission from erbium. In particular, the present invention provides a multi-modal lanthanide-porphyrin PDT agent (Er—R3) that are capable of killing the bladder tumor cells selectivity via 1O2 from porphyrin moiety and affording the fluorescence imaging simultaneously upon Er—R3 binding with the integrin ?v?3 isoform in bladder cancer cells.

Abstract: Described herein are compounds and compositions that modulate the activity of beta-lactamases. In some embodiments, the compounds described herein inhibit beta-lactamase. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.

Abstract: The present invention relates to compound (I) or a salt thereof which has a ROR?t inhibitory action. In the formula (I), each symbol is as defined in the specification.

Abstract: The present invention describes metal salen complexes having dianionic counterions. Such complexes can be readily precipitated and provide an economical method for the purification and isolation of the complexes, and are useful to prepare novel polymer compositions.

Abstract: The invention relates to a method for producing derivatives of O-?-glucosylated flavonoid, comprising at least one step of incubating a glucansucrase with a flavonoid and at least one sucrose, the flavonoid being a flavonoid which is monohydroxylated or hydroxylated in a non-vicinal manner on the B cycle. The invention also relates to novel O-?-glucosylated flavonoid derivatives, and to the use thereof.

Abstract: The invention relates generally to a calicheamicin molecule activated with a leaving group. The invention further relates generally to an antibody-drug conjugate comprising an antibody directly conjugated by a disulfide to one or more calicheamicin molecules.

Abstract: The invention provides compounds of the formula: wherein B is a nucleobase selected from the groups (a) to (d): and the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

Abstract: The present invention provides compounds according to formula I: and pharmaceutically acceptable salts thereof. For compounds of formula I, R1 and R2 are independently selected from the group consisting of H, —C(?O)—(CH2)2-aryl, and —C(?O)—(CH2)n—C(?O)—NH-aryl. The subscript n is from 2 to 6. R3 is selected from the group consisting of H and —C(?O)—O—R4; and R4 is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, arylalkyl, substituted arylalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl and substituted heteroalkyl. Compounds are provided wherein at least one of R1 and R2 is other than H. Pharmaceutical compositions, methods for inhibiting the growth of cancer cells, and methods for the treatment of cancer are also provided.

Abstract: This invention relates to a prodrug of the monophosphate nucleotide of the well-known oncology drug gemcitabine. Specifically, it relates to gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate when present as a single phosphate diastereoisomer and, in particular, it relates to the (S)-phosphate diastereoisomer which offers a remarkable and unexpected increase in solubility relative to the (R)-diastereoisomer. The (S)-phosphate epimer is also preferentially taken up into cyclodextrin solutions over the (R)-diastereoisomer.

Abstract: The present disclosure relates to compounds of the Formula (I), which are UBA5 inhibitors.

Abstract: The present invention relates to method and reagents for use in site-selective modification of protein and peptide. The site selective modification is a selective derivation of the amino functionality at the N-terminus of the protein or the polypeptide using the presence of a neighboring histidine amino acid to increase the reactivity of the N-terminal amino functionality. The modified proteins or peptides obtained by method of the invention may be used for imaging study or therapeutic uses.

Abstract: Herein is reported a method for producing a polypeptide in monomeric form comprising the following step: recovering the polypeptide in monomeric form from an ion exchange chromatography material by applying a solution comprising a non-ionic polymer and an additive.

Abstract: The present invention relates to a compound of formula (I) AA-AA-AA-R1-R2 (I) wherein, in any order, 2 of said AA (amino acid) moieties are cationic amino acids and 1 of said AA is an amino acid with a lipophilic R group, the R group having 14-27 non-hydrogen atoms; R1 is a N atom, which may be substituted by a branched or unbranched C1-C10 alkyl or aryl group, which group may incorporate up to 2 heteroatoms selected from N, O and S; and R2 is an aliphatic moiety having 2-20 non-hydrogen atoms, said moiety being linear, branched or cyclic. The invention further relates to formulations containing these compounds, solid supports having these compounds attached thereto, the use of these compounds in therapy, particularly as antimicrobial, anti-tumour or anti-biofilm agents and non-therapeutic uses of these compounds, particularly their use in inhibiting biofilm formation or removing a biofilm.

Abstract: The present invention relates to novel Ruthenium complexes and related borohydride complexes, and their use for (1) hydrogenation of amides (including polyamides) to alcohols and amines; (2) preparing amides from alcohols with amines (including preparing polyamides (e.g., polypeptides) by reacting dialcohols and diamines or by polymerization of amino alcohols); (3) hydrogenation of esters to alcohols (including hydrogenation of cyclic esters (lactones), cyclic di-esters (di-lactones) or polyesters); (4) hydrogenation of organic carbonates (including polycarbonates) to alcohols and of carbamates (including polycarbamates) or urea derivatives to alcohols and amines; (5) dehydrogenative coupling of alcohols to esters; (6) hydrogenation of secondary alcohols to ketones; (7) amidation of esters (synthesis of amides from esters and amines); (8) acylation of alcohols using esters; (9) coupling of alcohols with water to form carboxylic acids; and (10) dehydrogenation of beta-amino alcohols to form pyrazines.

Abstract: The disclosed peptidomimetic macrocycles modulate the activity of MCL-1. Myeloid cell leukemia 1 (MCL-1) is a protein that inhibits cell death. Peptidomimetic macrocycles, pharmaceutical compositions, and methods disclosed herein can be used for the treatment of disease in which MCL-1 is over-expressed, such as cancer. In particular, MCL-1-modulating peptidomimetic macrocycles disclosed herein can be applied in the setting of resistance to BCL-2 family inhibitors, which is often engendered by MCL-1 over-expression or hyper-activation.

Abstract: A therapeutic composition for treating brain injury comprising a polyarginine peptide of from 5 to 9 arginines, and further comprising 1 or more terminal cysteines. The composition is administered in therapeutically effective dosages prophylactically or as soon as possible post-injury in treating neuronal injury.

Abstract: The present invention relates to modified antimicrobial peptides which incorporate a histidine tag, are conjugated with a fatty acid and/or are PEGylated and their use in the treatment of microbial infections.

Abstract: The invention provides modified apelin polypeptides having increased stability, circulating half-life, and/or potency relative to the native apelin-13 polypeptide. Compositions comprising the modified apelin polypeptides and methods of using the polypeptides for treating cardiac disorders, such as heart failure, are also disclosed.

Abstract: This invention relates to modified antibiotic peptides, particularly for use in medicine. The invention further relates to composite and methods for destroying microorganisms, such as bacteria, viruses or fungi, and to methods for treating microbial infections. The object of the invention is to develop novel antibiotic peptides, particularly having enhanced antibiotic activity and an expanded spectrum of activity against other strains of bacteria, particularly gram-positive bacteria such as Staphylococcus aureus. According to the invention, the object is attained in a first aspect by a peptide according to claim 1.

Abstract: The invention relates to the field of pharmacology. In particular, it relates to novel analogs of apelin, and to the therapeutic uses thereof. Provided is cyclic apelin analog of the general formula X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14, comprising a Lanthionine bridge of the structure Ala-S-Ala or a methylLanthionine bridge of the structure Abu-S-Ala or Ala-S-Abu and wherein said (methyl)Lanthionine bridge is of the size i, i+3; i, i+4, i, i+5 or i, i+6.

Abstract: The invention relates to a method for inhibiting an ADAM protease, comprising inhibiting binding to an integrin-binding loop of a disintegrin domain in the ADAM protease. Also provided are cyclic peptides which inhibit binding to an integrin-binding loop of an ADAM protease, as well as associated pharmaceutical compositions, uses and methods of treatment.

Abstract: Template-fixed ?-hairpin peptidomimetics of the general formula wherein Z is a template-fixed chain of 12 ?-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or Pro, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to selectively inhibit the growth of or to kill microorganisms such as Pseudomonas aeruginosa. They can be used as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials, or as medicaments to treat or prevent infections. These ?-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid and solution phase synthetic strategy.

Abstract: The invention is directed to mosaic HIV 1 genes designed to induce T-cell responses.

Abstract: Modified capsid proteins containing at least a portion of hepatitis E virus (HEV) open reading frame 2 (ORF2) having one or more cysteine residues in a surface variable loop or the C-terminus of HEV ORF2, or a portion thereof, are provided. The modified capsid proteins can be used to form hepatitis E virus (HEV) virus like particles (VLPs) having cysteine functional groups exposed on the outer-surface. The exposed cysteine functional groups can be modified via their thiol reactive group. For example, a bioactive agent, such as a cell-targeting ligand, can be conjugated to the one or more cysteines for targeted delivery of chemically activated nanocapsids.

Abstract: Described herein is the generation of optimized H5N1 influenza HA polypeptides for eliciting a broadly reactive immune response to H5N1 influenza virus isolates. The optimized HA polypeptides were developed through a series of HA protein alignments, and subsequent generation of consensus sequences, based on human and avian H5N1 isolates. Provided herein are optimized H5N1 HA polypeptides, and compositions, fusion proteins and VLPs comprising the HA polypeptides. Further provided are codon-optimized nucleic acid sequences encoding the HA polypeptides. Methods of eliciting an immune response against influenza virus in a subject are also provided by the present disclosure.

Abstract: The present invention relates to a polypeptide comprising a mutant fragment of an outer surface protein A (OspA), a nucleic acid coding the same, a pharmaceutical composition (particularly for use as a medicament of in a method of treating or preventing a Borrelia infection) comprising the polypeptide and/or the nucleic acid, a method of treating or preventing a Borrelia infection and a method of immunizing a subject.

Abstract: The invention discloses a freeze-dried powder of high molecular weight silk fibroin, preparation process and use thereof. The freeze-dried powder is obtained from silk by degumming, dissolution, dialysis, centrifugation, high temperature and high pressure treatment and freeze-drying. A method of preparing silk fibroin microspheres with polyethylene glycol comprises mixing a silk fibroin solution of 1-30 wt % with a PEG solution of 10-60 w % and incubating the resulting solution. A controlled-release or sustained-release silk fibroin gel formulation includes a gel-state carrier and a drug dispersed/adsorbed therein, the carrier is a silk fibroin gel formed by blending with LMW-PEG.

Abstract: The present invention provides isolated Met e 1 polypeptides and nucleic acids encoding the isolated polypeptides that can prevent and/or alleviate an allergic response to shellfish tropomyosin. The polypeptides are based on the shrimp tropomyosin Met e 1 protein and have been modified to act as hypoallergens. The Met e 1 hypoallergens have low to no IgE reactivity or allergenicity and are useful for prophylactic and/or therapeutic treatment of shellfish allergy in subject in need thereof.

Abstract: The present invention relates to novel, specific-binding therapeutic and/or diagnostic polypeptides directed against the target of Swiss Prot Q16552 and novel, specific-binding therapeutic and/or diagnostic polypeptides directed against the target of Swiss Prot Q9NPF7. In addition, the present invention relates to novel, specific-binding therapeutic and/or diagnostic polypeptides directed against one or both of Swiss Prot Q16552 and Swiss Prot Q9NPF7. The invention also relates to nucleic acid molecules encoding such polypeptides and to methods for generation of such polypeptides and nucleic acid molecules. In addition, the invention is directed to compositions comprising the polypeptides, and therapeutic and/or diagnostic uses of these polypeptides.

Abstract: Novel peptide agonists of GLP-1 activity useful for lowering blood glucose levels. The novel peptides comprise variants of the GLP-1 or the exendin-4 polypeptide sequence and are pharmacologically active and stable. These peptides are useful in the treatment of diseases that benefit from regulation of excess levels of blood glucose and/or regulation of gastric emptying, such as diabetes and eating disorders.

Abstract: Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.

Abstract: Nucleic acid and protein sequences relating to a cation channel which is sperm-specific (CatSper1) are disclosed. The CatSper1 protein is shown to be specifically expressed in sperm and to be necessary for sperm motility. Nucleic acids, vectors, transformed cells, transgenic animals, polypeptides, and antibodies relating to the CatSper1 gene and protein are disclosed. Also provided are methods of in vitro fertilization and contraception, methods of identifying modulators of CatSper1 activity, methods of genotyping subjects with respect to CatSper1, and methods of diagnosing and treating CatSper1-mediated disorders, including infertility.

Abstract: The present disclosure features signal-regulatory protein ? (SIRP-?) polypeptides and constructs that are useful, e.g., to target a cell (e.g., a cancer cell or a cell of the immune system), to increase phagocytosis of the target cell, to eliminate immune cells such as regulatory T-cells, to kill cancer cells, to treat a disease (e.g., cancer) in a subject, or any combinations thereof. The SIRP-? constructs include a high affinity SIRP-? D1 domain or variant thereof that binds CD47 with higher affinity than a wild-type SIRP-?. The SIRP-? polypeptides or constructs include a SIRP-? D1 variant fused to an Fc domain monomer, a human serum albumin (HSA), an albumin-binding peptide, or a polyethylene glycol (PEG) polymer. Compositions provided herein include (i) a polypeptide including a signal-regulatory protein ? (SIRP-?) D1 variant and (ii) an antibody.

Abstract: Fusion polypeptides have an FGFR2 polypeptide and cDNAs encode such fusion polypeptides. Methods of diagnosing the presence of the fusion polypeptides or of a gene or RNA sequence coding therefore in a sample from a subject as well as methods of treatment of a tumor instructed by the latter diagnosis.

Abstract: Compositions are provided, which can be used as frameworks for the creation of very stable and soluble single-chain Fv antibody fragments. These frameworks have been selected for intracellular performance and are thus ideally suited for the creation of scFv antibody fragments or scFv antibody libraries for applications where stability and solubility are limiting factors for the performance of antibody fragments, such as in the reducing environment of a cell. Such frameworks can also be used to identify highly conserved residues and consensus sequences which demonstrate enhanced solubility and stability.

Abstract: An anti-hepatitis C virus E2 protein antibody or antigen-binding antibody fragment thereof has infection inhibiting activity against hepatitis C virus (HCV). An anti-hepatitis C virus E2 protein antibody or antigen-binding antibody fragment thereof includes a certain variable region, which have infection inhibiting activity against hepatitis C virus (HCV) and exhibits an escape mutant emergence suppressive property.

Abstract: A ligand includes each of the complementary-determining regions (CDRs) set forth in SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3 SEQ ID No. 4, SEQ ID No. 5 and SEQ ID No. 6 or any sequence having either number of substituted aminoacids within said sequences as indicated in the following, from 0 to 3 in CDR1 (SEQ ID No.1), from 0 to 2 in CDR2 (SEQ ID No.2), from 0 to 2 in CDR3 (SEQ ID No.3), from 0 to 1 in CDR4 (SEQ ID No.4), from 0 to 4 in CDR5 (SEQ ID No.5), from 0 to 2 in CDR6 (SEQ ID No.6), or aminoacids substituted with other aminoacids having equivalent chemical functions and properties, within said sequences SEQ ID No. 1 to SEQ ID No. 6.

Abstract: The invention provides chiral haptens (?)-3?-AmNic and (?)-N4N for use in generating antibodies in a patient specific for (?)-nicotine. The haptens can be conjugated to suitable carrier proteins and administered as an antigenic mixture, optionally comprising adjuvant(s), to a patient suffering from nicotine or tobacco addiction or habituation.

Abstract: Provided are binding polypeptides (e.g., antibodies), and drug conjugates thereof, comprising an Fc domain with an altered glycosylation profile and reduced effector function. In particular embodiment, the Fc domain comprises: an asparagine residue at amino acid position 298, according to EU numbering; and a serine threonine residue at amino acid position 300, according to EU numbering. Also provided are nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

Abstract: Compositions and methods for reducing inflammation in the central nervous system (CNS) of a mammal that has been subjected to a stroke, traumatic injury to the CNS such as traumatic brain injury (TBI), spinal cord injury (SCI), or having an autoimmune or CNS disease have been developed. The compositions and methods described herein include antibodies that specifically bind to at least one component (e.g., ASC, NALP1) in a mammalian inflammasome (e.g., the NALP1 inflammasome) and have use as treatments for SCI, TBI, stroke, and autoimmune and CNS diseases in a mammal. In a rodent model of SCI, therapeutic neutralization of ASC using a polyclonal antibody that specifically binds to ASC inhibited the inflammasome, reduced caspase-1 activation, XIAP cleavage, and interleukin processing, resulting in significant tissue sparing and functional improvement. Additionally, in a rodent model of TBI, neutralization of ASC after TBI reduced caspase-1 activation and XIAP cleavage.