7199results about "Sugar derivatives" patented technology

Provided are compounds of Formula I:nucleosides, nucleoside phosphates and prodrugs thereof, wherein R6 is CN, ethenyl, 2-haloethen-1-yl, or (C2-C8)-alkyn-1-yl. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections.

Provided is an antibody-drug conjugate for use in the treatment of cancer in which one or more KRAS mutants, particularly a KRAS G12V mutant, a KRAS G12D mutant, and a KRAS G12C mutant, are expressed. Also provided are a drug and a drug-linker conjugate for use in the antibody-drug conjugate.　The present inventors have produced an antibody-drug conjugate with which a heterocyclic compound represented by formula (II) and having an activity of inducing the decomposition of KRAS mutant proteins can be delivered to cancer in which EGFRs are expressed, the production being achieved by linking the compound to an anti-EGFR antibody. The present inventors have also discovered a drug-linker conjugate for use in the antibody-drug conjugate or a salt thereof. In cancer in which EGFRs are expressed, the antibody-drug conjugate induces the decomposition of one or more KRAS mutants, particularly a KRAS G12V mutant protein, a KRAS G12D mutant protein, and a KRAS G12C mutant protein, thereby inhibiting the KRAS mutants and exhibiting an anti-tumor effect.

This invention provides a halogenated compound for 5' end capping of nucleic acids and its applications, the compound being shown in formula (I). This invention also provides the uses and effects of the above-described compound on nucleic acid transcription and expression.

Among other things, the present disclosure provides designed DMD oligonucleotides, compositions, and methods of use thereof. In some embodiments, the present disclosure provides technologies useful for repairing mutant DMD transcripts by skipping exon 51 or exon 53, so that the transcript can be translated into an internally truncated but at least partially functional Dystrophin protein variant. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, provided technologies can alter splicing of a dystrophin (DMD) DMD transcript. In some embodiments, the present disclosure provides methods for treating diseases, such as muscular dystrophy, including but not limited to Duchenne muscular dystrophy, Becker's muscular dystrophy, etc.

The present disclosure features useful oligonucleotide compositions and methods related thereto. The present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g. modifications of sugar, base and / or internucleotide linkages) or patterns thereof, can have a significant impact on oligonucleotide properties and activities. The present disclosure also provides methods to treat disorders for which deamination of an adenosine in an mRNA produces a therapeutic result, e.g., in a subject in need thereof.

The present disclosure includes ionizable lipids suitable for lipid nanoparticle compositions and pharmaceutical formulations thereof. The lipids have general formula (I).

Compounds having the structure of Formula (I): or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof; wherein R1, R2, R3, R4, R5, L1, L2, a and z are as defined herein, are disclosed. Use of these compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds, and methods for their use and preparation are also provided.

The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.

The invention discloses a method for extracting and purifying flavone in litsea coreana through an ultrasonic-assisted eutectic solvent, and belongs to the technical field of green processing of natural products. The invention provides a method for efficiently preparing litsea coreana flavone by integrating computer prediction, green solvent extraction and resin purification technologies. The method comprises the following steps: firstly, calculating and screening a deep eutectic solvent system with the highest affinity with the litsea coreana flavone on the basis of a COSMO-RS theoretical model, then coupling the optimized DES with an ultrasonic-assisted extraction (UAE) technology, and through the synergistic effect of the DES and the UAE technology, remarkably improving the extraction rate of the litsea coreana flavone and furthest keeping the biological activity of a target component; then, a macroporous resin dynamic adsorption-desorption purification process is linked, so that high-selectivity enrichment and impurity removal of the flavonoid compounds in the crude extract are realized, a high-purity product is obtained, and a complete process route from intelligent screening, efficient extraction to precise purification is finally formed.

The present disclosure provides multivalent molecules (e.g., compositions of Formula (I), an ionized form thereof, an isomer thereof, or a salt thereof. The present disclosure further provides methods for the use of the compositions, e.g. in the sequencing of poly-nucleic acid molecules.

The invention provides a benzofuranone compound as well as a pharmaceutical composition and application thereof, and relates to the technical field of medicines. The benzofuranone compound is a compound as shown in a formula I, a stereoisomer thereof, a tautomer thereof, a crystalline hydrate thereof, a solvate thereof, a prodrug thereof or a pharmaceutically acceptable salt thereof. The benzofuranone compound and the pharmaceutical composition and the pharmaceutical preparation prepared from the benzofuranone compound can prevent or treat organ injury diseases, and have good treatment effects in kidney injury, liver injury, lung injury, brain injury and heart injury.

Described herein are programmable DNA proteolytic target chimera complexes that can be used both for the direct treatment of cancer by inhibiting biochemical pathways that are overexpressed in cancer cells, and for the indirect treatment of cancer by recruiting the E3 ligase complex to engage with a protein of interest or a mutant thereof and initiating proteolysis. Also described herein are methods of using the complexes in the treatment of cancer, as well as compositions comprising the complexes.

The invention provides a double-target degradation molecule based on a functionalized nucleic acid connexon and application thereof, and relates to the technical field of biological medicine, the double-target degradation molecule comprises an E3 ubiquitin ligase ligand at one end, a first target protein ligand at the other end, and the functionalized nucleic acid connexon located between the E3 ubiquitin ligase ligand and the first target protein ligand; the functionalized nucleic acid linker is a nucleotide sequence capable of specifically recognizing and combining a second target protein or a coding gene thereof, so that the protein level degradation of the first target protein and the nucleic acid level or expression level inhibition of the second target protein / gene are realized in the same molecule. Functionalized nucleic acid and a PROTAC strategy are organically combined, single-molecule double-target collaborative intervention is achieved, targeting efficiency and treatment potential are improved, higher flexibility and expandability are provided in synthesis and design, and a new molecular platform and technical route are provided for multi-target accurate treatment.

The invention relates to a ligand-effector moiety provided with at least one saponin and antibody-effector moiety provided with at least one saponin. An aspect of the invention is a composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention. The invention also relates to an antibody-drug conjugate comprising covalently linked saponin and to an antibody-oligonucleotide conjugate comprising covalently linked saponin. An aspect of the invention relates to a pharmaceutical composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin, for use as a medicament. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention for use in the treatment or prophylaxis of a cancer.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the complement component C3 gene (C3). The invention also relates to methods of using such RNAi agents to inhibit expression of a C3 gene and to methods of preventing and treating a C3-associated disorder, e.g., cold agglutinin disease (CAD), warm autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH), lupis nephritis (LN), bullous pemphigoid, Pemphigus, e.g., Pemphigus vulgaris (PV) and Pemphigus foliaceus (PF), and C3 glomerulopathy.

Disclosed herein are activatable inactive sonosensitizer compounds, referred to as locked sonosensitizer compounds, designed with a detachable stimuli-responsive tether acting as a trigger or safety, as these compounds restore their inherent sonosensitization activity upon the detachment of the tether. The invention further encompasses pharmaceutical compositions comprising the same, offering a strategic approach to sonodynamic therapy, whereas the compounds and compositions are formulated to be administered and applied under favorable conditions, enhancing their efficacy in the context of therapeutic applications, since the therapeutic methods presented herein are more versatile and efficient compared to presently known SDT methods due to the controlled activation of the sonosensitizer.

A pathogen surrogate, formed by a DNA tag or bar code and a carrier, is described for use in the validation and verification of sanitation, such as in food processing operations and for wash water systems for fresh produce. The carrier material is selected so that the pathogen surrogate mimics the behavior of a pathogen when subjected to a sanitation operation. One or more surrogates can be introduced in to an environment, which is then subjected to sanitation process, followed by a detection process using the DNA tag of the surrogate.

The disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising one or more chemically modified nucleobases. In some embodiments, the dsDNA molecule is circular and comprises a first strand and a second strand, wherein the first strand comprises one or more chemically modified nucleobases, and the second strand is free of chemically modified nucleobases. In some embodiments, the dsDNA molecule comprises a promoter sequence and an effector sequence that encodes an effector.

The technology described herein relates to 5'-modified nucleosides, nucleotides, oligonucleotides and double-stranded RNAs, e.g., siRNAs, and kits comprising them and methods of their use for inhibiting target genes.

The instant disclosure relates to lipid particles that harbor cationic lipids, the particles found to be capable of delivering associated cargoes - particularly nucleic acid cargoes when formulated as nucleic acid-lipid particles - intracellularly to skin tissue cells when administered topically to a subject. The instant disclosure provides compositions comprising such lipid particles, optionally in association with a therapeutic agent (e.g., a therapeutic mRNA and / or nucleic acid controller system), as well as methods and kits for delivering a lipid particle-associated therapeutic agent and / or for treating or preventing a disease or disorder, e.g., a skin disease or disorder, in a subject, using one or more lipid particle compositions provided herein.

The utility model belongs to the technical field of sugar alcohol preparation, and relates to a system for co-producing L-arabinose and caramel pigment by using xylose chromatography raffinate, which comprises a raw material tank, a nanofiltration membrane separator, a chromatography separation device, an evaporation concentration tank, a crystallization tank, a centrifugal separator and a dryer which are sequentially communicated by pipelines, and the browning reaction assembly is used for mixing the raffinate and the centrifugal mother liquor and then carrying out browning reaction treatment to prepare caramel pigment. The chromatographic separation device is used for separating an extracting solution and raffinate from the flowing nanofiltration permeate, the evaporation concentration tank and the crystallizing tank are used for concentrating and crystallizing the flowing extracting solution into massecuite, the centrifugal separator is used for separating the flowing massecuite into moist sugar and centrifugal mother liquor, and the dryer is used for drying the flowing moist sugar into L-arabinose crystals. According to the utility model, raffinate and centrifugal mother liquor are mixed to prepare a caramel pigment liquid product, so that a caramel pigment additional product is obtained while the utilization rate of saccharide resources is improved.

The application provides a Huangdache oligosaccharide with GLP-1 agonist activity and application thereof, and belongs to the technical field of medicines. 3 The oligosaccharide component ELYP-3 has a molecular weight of 3.2*10 3 Da, and the molar ratio of monosaccharides is rhamnose:galacturonic acid:glucose:galactose:arabinose = 1:32.42:45.37:9.11:6.54. The Huangdache oligosaccharide fragment obtained by glycosidase degradation has significant hypoglycemic and weight loss activities, the preparation process is simple, specific and green, and provides scientific basis and theoretical support for the development of natural GLP-1 agonists. Meanwhile, the functional oligosaccharide provides a wide application prospect for the development of medicines with blood glucose regulation.

The invention belongs to the technical field of medicines, and discloses a near-infrared cyanine probe for detecting penicillin G acylase as well as a preparation method and application of the near-infrared cyanine probe. According to the research, a near-infrared fluorescent probe Cy-NEO-PA responding to penicillin G acylase (PGA) is developed, so that the influence of environmental factors on the formation of an acinetobacter baumannii biological membrane is observed. Research results show that glucose inhibits the generation of PGA to enhance the formation of a biological membrane, while phenylacetic acid (PAA) stimulates the generation of PGA and inhibits the formation of the biological membrane. The observation results highlight the excellent capability of Cy-NEO-PA in accurately measuring PGA kinetics, and reveal the key effect of PGA in biological membrane development. In addition, the Cy-NEO-PA has good biocompatibility, strong active oxygen generation, efficient photo-thermal conversion and bacterial targeting ability, so that the Cy-NEO-PA becomes a promising drug for resisting bacterial infection and promoting wound healing through photo-thermal / photodynamic therapy.

The invention relates to the technical field of well cementation materials and provides well cementation cement stone based on water-based benzoxazine resin as well as a preparation method and application of the well cementation cement stone. The well cementation cement stone is prepared from the following components in parts by mass: 400-600 parts of quartz sand, 4-6 parts of a retarder, 4-6 parts of a fluid loss agent, 1-2 parts of a suspension stabilizer, 1-2 parts of a dispersant, 4-6 parts of a high-temperature-resistant water-based benzoxazine monomer and 40-50 parts of water, and the high-temperature-resistant water-based benzoxazine monomer is prepared from a phenolic compound, primary amine and formaldehyde through Mannich reaction. Resin formed by the prepared benzoxazine monomer has improved mechanical properties at a high temperature of 150-200 DEG C, the mechanical properties and high temperature resistance of well cementation cement at a high temperature are significantly improved by filling pores of set cement and optimizing cement components, the benzoxazine monomer in a cement slurry system does not affect the fluidity of cement slurry, and the well cementation cement has a good application prospect. Meanwhile, the high-temperature strength of set cement can be remarkably enhanced, and the cement is suitable for well cementation of high-temperature deep wells.

Exemplary olfactory delivery scaffolds may include 1) an olfactory targeting component, stimulant, or odorant that is recognized by the olfactory nerves via, for example, a smell response, 2) a molecule with biological activity, a therapeutic component, and / or drug (sometimes collectively referred to herein as a “therapeutic component”), and 3) a linker component that links the olfactory targeting component and therapeutic component together. The olfactory delivery scaffolds may be used to deliver a molecule with biological activity and / or a therapeutic component to a subject's neurological system through the olfactory pathway and pharmaceutical compositions useful in the treatment of neurological and / or neurodegenerative diseases.

Provided herein is a method for efficiently capping RNA in vitro. In some embodiments the capping reaction may be done at high temperature using Vaccinia capping enzyme or a variant thereof. In other embodiments, the capping reactions may comprise a capping enzyme from a large virus of amoeba, e.g., Faustovirus, mimivirus or moumouvirus, or a variant thereof. Compositions and kits for practicing the method are also provided.

The invention discloses a toughening agent, a toughened epoxy resin adhesive and a preparation method and application thereof. The toughening agent is obtained by carrying out esterification reaction on components including a phenolic compound containing a polyphenol skeleton and an anhydride compound containing a long-chain alkyl structure. The raw materials used by the toughening agent are bio-based molecules and have excellent renewability, the toughening agent is high in toughening efficiency, the impact strength of the epoxy resin adhesive can be effectively improved under the condition of low addition amount, and meanwhile, the bonding strength and the hydrothermal durability of the epoxy resin adhesive can be improved.

The invention belongs to the field of natural product extraction, and relates to a method for extracting and separating flavonoid compounds from Artemisia chrysantha, which comprises the following steps: carrying out reflux extraction on the dry overground part of Artemisia chrysantha by using 70% ethanol, loading to a balanced D101 macroporous adsorption resin column, sequentially eluting by using water, a 20% ethanol aqueous solution, a 50% ethanol aqueous solution and a 70% ethanol aqueous solution, and collecting the eluent. Four fractions from Fr. I to Fr. IV are obtained; respectively carrying out polyamide column chromatography separation on Fr.II to Fr.IV, and sequentially eluting with a 20% ethanol aqueous solution, a 50% ethanol aqueous solution and a 70% ethanol aqueous solution to respectively obtain three fractions; and further purifying the Fr.II-1, the Fr.II-2, the Fr.III-1, the Fr.III-2, the Fr.III-1 and the Fr.III-3 by virtue of a Sephadex LH-20 column, so as to finally obtain seven flavonoid compounds. According to the method, only the ethanol water low-toxicity solvent is used for extraction and preparation, organic solvents with high toxicity are not used, the method is green and environment-friendly, the extraction efficiency is high, the number of extracted compounds is large, chemical components of the artemisia europaea medicinal material are enriched, the resource source of active components is widened, and a foundation is laid for follow-up research.

The invention discloses a near-infrared two-region activatable probe as well as a preparation method and application thereof. The near-infrared second-region activatable probe comprises a near-infrared second-region fluorescent light-emitting unit and an analyte specific response unit; the near-infrared second-region light-emitting unit comprises a hemicyanine fluorophore structure; when the analyte specific response unit is chemically coupled with the near-infrared second-region light-emitting unit, the intramolecular charge transfer process of the light-emitting unit can be inhibited, and fluorescence quenching is caused; the analyte specific response unit is separated from the light-emitting unit after being subjected to specific reaction with an analyte, so that fluorescence is activated. The near-infrared two-region hemicyanine fluorophore selected by the near-infrared two-region activatable probe has higher fluorescence quantum efficiency, and the near-infrared two-region probe which can be activated by a specific analyte and has a high on-off ratio can be constructed by introducing an analyte specific response unit, so that high-temporal-spatial-resolution fluorescence detection of deep tissues can be realized; the method has a wide application prospect in the field of biomedical detection.