Abstract: The present invention relates to a compound of the Formula: or a pharmaceutically acceptable salt thereof. The compound of the present invention inhibits Pol?. This novel therapeutic compound is therefore useful for the treatment and/or prevention of diseases and conditions in which Pol? activity is implicated, such as, for example but not limited to, the treatment and/or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compound defined herein, to processes for synthesising the compound and to their use for the treatment of diseases and/or conditions in which Pol? activity is implicated.

Abstract: The present invention relates to a compound of the Formula: or a pharmaceutically acceptable salt thereof. The compound of the present invention inhibits Pol?. This novel therapeutic compound is therefore useful for the treatment and/or prevention of diseases and conditions in which Pol? activity is implicated, such as, for example but not limited to, the treatment and/or prevention of cancer. The present invention also relates to pharmaceutical compositions comprising the novel therapeutic compound defined herein, to processes for synthesising the compound and to their use for the treatment of diseases and/or conditions in which Pol? activity is implicated.

Abstract: The present invention belongs to the technical field of biomedicine, and particularly relates to thiophene-phenothiazine compounds and a synthesis method thereof, as well as application thereof in preparation of phototherapy medicines. The present invention provides thiophene-phenothiazine compounds or pharmaceutically acceptable salts thereof, in the structure of which a thiophene structure is successfully fused to a phenothiazine framework, providing a novel molecular scaffold. The special structure exhibits excellent photodynamic activity, has strong wavelength absorption and good photostability in a near-infrared region, and can efficiently generate ROS under red light, and therefore, the thiophene-phenothiazine compound or the pharmaceutically acceptable salt thereof can be used as a photosensitizer. The thiophene-phenothiazine compounds of the present invention have strong photocytotoxicity and high phototherapeutic indexes, exhibit strong photodynamic anti-tumor activity without obvious side effects.

Abstract: The present application relates to a pyrimidopyran compound, and specifically discloses a compound as represented by formula (III), and a pharmaceutically acceptable salt thereof.

Abstract: The present disclosure relates to a fused tetracyclic compound, a preparation method therefor and an application thereof in medicine. Specifically, the present disclosure relates to a fused tetracyclic compound as shown in general formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and use thereof as a therapeutic agent, in particular use thereof in preparation of drugs for inhibiting KRAS G12D. The groups in general formula (I) are as defined in the description.

Abstract: Disclosed are amino-substituted heteroaromatic compounds such as 4-amino-quinazolines, pharmaceutically acceptable salts of the compounds, and pharmaceutical compositions thereof. Also disclosed are methods of treating or preventing cancer using the amino-substituted heteroaromatic compounds, pharmaceutically acceptable salts of the compounds, and pharmaceutical compositions thereof.

Abstract: The invention relates to pharmaceutical compositions comprising the compound of Formula I, and new methods and uses pertaining thereto, and pharmaceutical compositions thereof, such as methods of use in the treatment of diseases involving the 5-HT receptor, the serotonin transporter (SERT), and/or pathways involving dopamine D2 receptor signaling, sodium channel activity, and/or norepinephrine transporter activity.

Abstract: A highly efficient and safe N-cyanation and N-phosphorylation reagent for the de novo synthesis of pharmaceutically acceptable cyclocreatine and salts was achieved using trichloroacetonitrile in lieu of highly toxic cyanogen bromide (CNBr) for generating the required cyclocreatine (CCr) intermediates, followed by highly effective N-phosphorylation through pH control using phosphoryl chloride with high conversion to the corresponding cyclocreatine phosphate (CCrP) targets. A continuous flow reactor system was engineered to improve the efficiency of the process and deliver a product with improved yield, safety, and cost efficiency.

Abstract: Provided herein, in certain embodiments, are compounds of Formula I: or a pharmaceutically acceptable salt or a solvate thereof, compositions comprising a compounds of Formula I, or a pharmaceutically acceptable salt or a solvate thereof, and uses thereof such as in treating certain diseases or disorders (e.g., cancer, fibrosis, chronic inflammation).

Abstract: Methods of treating presbyopia or cataract in a subject in need thereof are provided. The methods require administering to the subject an effective amount of a composition comprising a compound that inhibits the formation or dissolves high molecular weight aggregates of human ?-A-crystallin. Compositions containing certain compounds are believed to be also effective in the treatment of transthyretin (TTR)-associated amyloidosis, Prion, Creutzfeldt-Jakob, Gerstmann-Sträussler-Scheinker disease and Ankyloblepharon-ectodermal dysplasia-cleft lip/palate syndrome.

Abstract: Methods of preparing compounds useful as water soluble dyes are disclosed. Specifically, the compounds have the following Structure (I): (I) or a stereoisomer, tautomer or salt thereof, wherein L1, L2, L3, R1, R2, and M are as defined herein.

Abstract: An organometallic compound represented by Formula 1: M1(L1)n1(L2)n2??Formula 1 wherein, M1 is a transition metal, L1 is a ligand represented by Formula 1A, L2 is a ligand represented by Formula 1B, and n1 and n2 are each independently 1 or 2, wherein i) X45 is C(R45) and X46 is C(R46), wherein R45 and R46 are bonded together to form a group represented by Formula 2, ii) X46 is C(R46) and X47 is C(R47), wherein R46 and R47 are bonded together to form a group represented by Formula 2, or iii) X47 is C(R47) and X48 is C(R48), wherein R47 and R48 are bonded together to form a group represented by Formula 2; ring CY4 and ring CY5 are condensed with each other, and the remaining descriptions of Formulae 1A, 1B, and 2 are as provided herein.

Abstract: Methods of synthesizing crystalline metal-organic frameworks (MOFs) having polytopic organic linkers and, cations, where each linker is connected, to two or more cations, are provided. In the disclosed methods, the linkers are reacted with one or more compounds of formula MnXm, where each M is independently cationic Be, Mg, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Zr, Nb, Mo, Ru, Rh, Pd, Cd, or Hf, X is anionic, n and m are integers. The reaction is performed in the presence of a salicylate, salicylamide, 1,3-phthalate, or hydroxybenzoate based modulator.

Abstract: The present application relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, and intermediates thereto. The application also provides pharmaceutical compositions comprising compounds of the present invention and methods of using said compounds or compositions in the treatment of and immunization for infectious diseases.

Abstract: A method for purifying a nucleotide-based substance; including a protecting group introduction step of introducing a hydrophobic protecting group represented by the following formula (P1) or (P2) into a nucleotide-based substance to produce a hydrophobic nucleotide-based substance; an isolation and purification step of isolating and purifying the hydrophobic nucleotide-based substance under a hydrophobic environment; and a deprotection step of deprotecting the hydrophobic protecting group from the hydrophobic nucleotide-based substance to produce the nucleotide-based substance, wherein R1 represents a linear or branched alkyl group having 1 to 30 carbon atoms, R4 represents hydrogen or a linear or branched alkyl group having 1 to 10 carbon atoms, R2, R3, R5 and R6 represent hydrogen, a linear or branched alkyl group having 1 to 10 carbon atoms, or the like, and may be the same or different; and * means a bond with a nucleotide-based substance.

Abstract: Provided is a method for purifying sucralose-6-acetate, including: preparation: providing a saturated solution of crude sucralose-6-acetate in ethyl acetate that is heated to a predetermined temperature; gradient crystallization: subjecting the saturated solution to multiple cooling crystallization and filtration, and collecting crude sucralose-6-acetate obtained after the multiple cooling crystallization and filtration, where during each cooling crystallization process, a low-polarity solvent is added dropwise to the saturated solution to reduce a polarity of the saturated solution during crystallization step by step; and purification: subjecting a collected crude sucralose-6-acetate to recrystallization for purification by using a mixed solution of ethyl acetate and the low-polarity solvent to obtain fine sucralose-6-acetate of high purity.

Abstract: A series of deuterated nucleoside compounds are compounds represented by formula (IV), and stereoisomers or pharmaceutically acceptable salts thereof.

Abstract: Aspects of the present disclosure provide methods for the chemical synthesis of cytidine-5?-monophospho-N-glycyl-sialic acid (GSC).

Abstract: Provided herein are lithium-including reagents useful in solid phase synthesis. Provided herein are improved methods of oligonucleotide synthesis on UnySupport solid support.

Abstract: This invention provides a structure-based design method for making antisense oligonucleotides (ASOs) and ASOs made by this method. ASOs are an emerging class of drugs that are especially suitable for fighting a wide range of diseases. They are single-stranded synthetic oligonucleotides that specifically bind target RNAs and elicit desired biological and therapeutic effects. Conventional ASO design strategies do not adequately address this problem. The instant invention includes structure-based ASO designs that target RNAs critical in a variety of diseases.

Abstract: Provided are novel glucose derivatives and an anticancer agent using the same. The glucose derivatives according to the present invention consist of an L-glucose derivative represented by general formula (1) and a D-glucose derivative represented by general formula (2). In formula (1): XL2 represents an —SAuRL2 group; and XL1, XL3, XL4 and XL5 independently represent an —ORL1 group, an —NH2 group or a fluorine atom. RL2 represents a ligand, and RL1 represents a hydrogen atom or an organic group. In formula (2): XD2 represents an —SAuRD2 group; and XD1, XD3, XD4 and XD5 independently represent an —ORD1 group, an —NH2 group or a fluorine atom. RD2 represents a ligand, and RD1 represents a hydrogen atom or an organic group. The anticancer agent according to the present invention comprises at least one of the aforesaid glucose derivatives.

Abstract: The present invention is directed to a process for the preparation of ?9,11 steroids by deoxygenation of 9,11-epoxy steroids using HI. The disclosed process selectively forms ?9,11 steroids such as Vamorolone and can also be used for steroid synthesis of ?9,11 steroids in pharmaceutical purity.

Abstract: The present invention provides compounds represented by Formula I, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates or combination thereof, The invention also provides pharmaceutical compositions comprising these compounds and methods of using this compounds for treating FXR-mediated or TGR5-mediated diseases or conditions.

Abstract: The invention pertains to methods of purifying fusion proteins, in particular TNFR:Fc fusion proteins. Methods disclosed herein can be used to produce highly pure TNFR:Fc fusion proteins (e.g., etanercept) having a biological activity by removing hard to separate product related impurities such as clipped and/or mis-fold/aggregated TNFR:Fc fusion proteins.

Abstract: Provided herein is an environmentally compatible detergent for use in purification of a recombinantly produced bio-therapeutic. The environmentally compatible detergent includes Laureth-9 and can be used for viral clearance, cell lysis, and removal of impurities such as host cell proteins an endotoxins. Advantageously, Laureth-9 does not adversely impact product quality.

Abstract: The disclosure is directed to systems and methods for purifying proteins containing an Fc region, such as antibodies or Fc fusion proteins. The system includes one or more filler molecules comprising a linear hydrocarbon chain conjugated to a peptide amino acid sequence, and one or more ligand molecules comprising a linear hydrocarbon chain, a peptide amino acid sequence, a linker, and a Z33 peptide of Staphylococcus aureus Protein A. The filler molecules and ligand molecules self-assemble into immunofibers (IFs) under physiological conditions.

Abstract: Therapeutic compounds of the invention comprise peptidomimetics, including those of formula (I), which has been prepared using solid-phase peptide synthesis. It is useful in the treatment of a cancer, including, for the treatment of a pancreatic cancer, a lung cancer or a colorectal cancer, further, including, a treatment for a pancreatic ductal adenocarcinoma.

Abstract: The present technology provides disulfide-containing lipopeptides of Formula I. Such lipids may be incorporated into lipid nanoparticles for delivery of nucleic acids, nucleotides (e.g., NAD+ or NADH), polypeptides (including proteins), and complexes of proteins and nucleic acids, e.g., Cas9 RNP. The present technology also provides methods for delivering the nanoparticles to a cell and methods of treating a condition or disorder using the lipid nanoparticles.

Abstract: The present disclosure provides a compound. The compound is a compound shown in formula (1) or a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt, or a prodrug of the compound shown in formula (1). The compound shown in formula (1) can significantly inhibit Mpro or inhibit coronavirus replication, and has excellent metabolic stability.

Abstract: The present disclosure concerns agents and their use in the treatment of endocrine, nutritional and/or metabolic diseases in a mammal. The disclosure furthermore concerns novel peptide fragments.

Abstract: Disclosed herein are NorA peptide inhibitors, protein scaffolds including the NorA peptide inhibitor, and antibody-based molecules that bind NorA, as well as compositions containing the same. Also disclosed are combinations therapeutic agents that include an antibiotic and/or biocide; and a NorA inhibitor, protein scaffold, or antibody-based as disclosed herein. Use of these agents for treating a Staphylococcus aureus infection, potentiating the therapeutic efficacy of an antibiotic or biocide, diagnosing a S. aureus infection, and detecting NorA in a non-clinical biological sample are also disclosed.

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: Disclosed herein is a short peptide consisting of an amino acid sequence at least 85% identical to SEQ ID NO: 1. According to some embodiments of the present disclosure, the short peptide consists of an amino acid sequence 100% identical to SEQ ID NO: 1, 2, 3 or 4. According to certain embodiments of the present disclosure, the short peptide is useful in treating neurological diseases via enhancing neurite outgrowth. Accordingly, also disclosed herein are a pharmaceutical composition comprising the short peptide, and uses thereof in treating neurological diseases.

Abstract: The invention provides novel antibacterial compounds of formulae IA, IB and IC as defined herein. Optionally, the antibacterial compounds can be bonded to a delivery agent that is capable of bonding to one or more structures on a bacterial cell membrane. The invention also provides the use of such compounds in treating or preventing bacterial infections, and processes for their synthesis.

Abstract: The present invention relates to a peptide ligand that specifically binds to carbonic anhydrase IX (CAIX), a peptide construct comprising the ligand, and a use thereof. The CAIX-binding peptide ligand of the present invention includes D-amino acids, so it is stable in the body and has high binding specificity to CAIX. And the linear or cyclic CAIX-binding peptide construct comprising the ligand can bind to CAIX with high affinity in the body. Therefore, it is useful for diagnosis, prevention, suppression or treatment of diseases mediated by CAIX.

Abstract: The present invention relates to peptides, antigen binding proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer, especially of fibrolamellar hepatocellular carcinoma (FL-HCC). The present invention furthermore relates to tumor-associated T-cell peptide epitopes and recombinant T-cell receptors that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients.

Abstract: The invention relates to an isolated non-naturally occurring protein comprising the amino acid sequence as set forth in SEQ ID NO: 1, and wherein the amino acid in position 8, 47, 209 and/or 354 is substituted by any amino acid different from the amino acid indicated at that position in said sequence SEQ ID NO: 1.

Abstract: The invention relates to an isolated non-naturally occurring protein comprising the amino acid sequence as set forth in SEQ ID NO: 1, and wherein the amino acid in position 8, 47, 209 and/or 354 is substituted by any amino acid different from the amino acid indicated at that position in said sequence SEQ ID NO: 1.

Abstract: The present invention provides methods and compositions comprising an adeno-associated virus (AAV) capsid protein, comprising one or more amino acids substitutions, wherein the substitutions introduce a new glycan binding site into the AAV capsid protein.

Abstract: The present disclosure relates to functionalised polypeptides, nanoparticles and their 5 uses thereof. The functionalised polypeptide comprises polylysine functionalised with guanidinium moieties, wherein the polypeptide is about 50% to about 98% functionalised. The number of guanidinium functionalised lysine monomeric units is 5 to 100, and the number of lysine monomeric units is 1 to 50. The functionalised polypeptides and nanoparticles can be used for treating a microbial infection or for 10 treating cancer.

Abstract: The inventors have identified residues within variant 2 and variant 3 of meningococcal fHpb which can be modified to enhance their properties.

Abstract: The present invention relates to polypeptides, which are capable of inducing and/or enhancing secretion of IL-10 from human cells. Accordingly, the present invention provides polypeptides, which stimulate IL-10 release from human immune cells. The present invention also relates to nucleic acids encoding such polypeptide, cells expressing such polypeptide, respective pharmaceutical compositions and uses thereof.

Abstract: The present invention is directed to a modified clostridial neurotoxin comprising a botulinum neurotoxin A (BoNT/A) Hcc domain, wherein the Hcc domain comprises a modification of methionine 1144 (MI 144), and wherein the modification increases oxidative resistance of the modified clostridial neurotoxin when compared to an otherwise identical clostridial neurotoxin lacking the modification. Also provided are (inter alia) corresponding methods for producing the same, methods for selecting oxidation resistant clostridial neurotoxins, nucleic acids encoding the same, and therapeutic uses of said modified clostridial neurotoxins.

Abstract: Disclosed are protein-like polymers and uses thereof. The protein-like polymers generally comprise a polymer of formula (FX1). The polymer of formula (FX1) in some aspects comprises a peptide having similarity or homology to a tandem repeat peptide sequence found in a natural protein or natural peptide, and/or the polymer of formula (FX1) in some aspects comprises a peptide comprising at least one catechol residue.

Abstract: Improved Red Fluorescent Proteins (RFPs), nucleic acids encoding the improved RFPs, and methods of generating improved RFPs are described. The improved RFP can be used to form fusion molecule and can be used in applications for which fluorescent proteins are used.

Abstract: Proteins, nucleic acids encoding the proteins, compositions comprising the proteins, and methods are provided. The proteins have the ability to be self-targeted to ICAM-1 and, if desired, enzymatically-released at acidic pH. The ICAM-1-targeting peptides are provided as single copies or multiples repeats, and can be separated by linkers from the enzyme segment, from which the ICAM-1 targeting peptides can be released, if desired, at acidic pH. These fusion proteins enhance the activity of the enzyme segment within or liberated from the fusion protein, and provide increased recognition and targeting of diseased organs, transport from the bloodstream across the endothelium into said diseased organ, and intracellular uptake and lysosomal trafficking by cells in them, both in peripheral tissues and the central nervous system. Representative nucleotide and amino acid sequences of these fusion proteins, as well as in vitro, cellular, and in vivo animal data are provided.

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Abstract: A novel class of fusion proteins to recruit a cell's innate chaperone mechanism, specifically the Hsp70-mediated system, to specifically reduce TDP-43-mediated protein aggregation and associated proteopathies is disclosed.

Abstract: Methods, systems, compositions and strategies for the delivery of WW domain-containing fusion proteins into cells in vivo, ex vivo, or in vitro via ARMMs are provided. Methods, systems, compositions and strategies for the delivery of Cas9 proteins and/or Cas9 variants into cells in vivo, ex vivo, or in vitro via fusion to ARMM associated proteins (e.g., ARRDC1 or TSG101) are also provided.

Abstract: The present disclosure relates to compositions and methods for treatment of degenerative conditions of large weight-bearing joints, such as osteoarthritis, by intra-articular delivery of a codon-modified IL-1Ra encoding gene.