6233 results about "Small molecule" patented technology

Compounds of Formula (I) or their pharmaceutically acceptable salts can inhibit the G12C, G12D, G12V, and / or G13D mutants of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Compounds of Formula (I) or their pharmaceutically acceptable salts can inhibit the G12C, G12D, G12V, and / or G13D mutants of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

The invention discloses an embolism part for peripheral arteriovenous vessels, the embolism part comprises an anchoring part and a blocking part fixedly connected with the anchoring part, the blocking part adopts polyurethane shape memory foam, the expansion rate of the polyurethane shape memory foam is 50-100 times, and a preparation method of the polyurethane shape memory foam comprises the following steps: step 1, preparing a polyurethane shape memory foam material; the preparation method comprises the following steps: preparing a polyurethane acrylate prepolymer from macromolecular polyol, diisocyanate, a chain extender containing disulfide bonds, other micromolecular chain extenders and an acrylate end-capping reagent; and 2, uniformly mixing the polyurethane acrylate prepolymer, a foaming agent, a foaming promoter and a photoinitiator to obtain a foaming solution, and sequentially carrying out light curing and foaming on the foaming solution to obtain the polyurethane shape memory foam. According to the embolism part, the polyurethane shape memory foam is adopted as the blocking part, the blocking part applies radial acting force to the wall of the blood vessel all the time based on the expansion trend of the blocking part, and the blocking part and the anchoring part jointly act and can be stably maintained in the blood vessel.

Compounds or their pharmaceutically acceptable salts can modulate the G12D mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds disclosed herein or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

The present invention provides a class of small molecule compounds for targeted degradation of a pan-KRAS protein, a preparation method therefor, and use thereof as a therapeutic agent for preventing and / or treating cancer. The compound of the present invention can effectively degrade and / or inhibit the pan-KRAS protein in cells, and can be used for preparing a drug for treating and / or preventing related diseases or disorders caused by pan-KRAS mediation.

The invention discloses an extraction preparation method and application of algae micromolecule PDRN, and relates to the technical field of biology. The invention establishes a process for extracting PDRN from microalgae, which comprises the following steps: carrying out cell disruption on microalgae liquid, and removing cell debris to obtain filtrate; the filtrate is subjected to DNA dissolution, DNA separation and DNA purification, and a PDRN solution is obtained; wherein the dry weight of the microalgae in the algae liquid is 0.1 to 0.333 g / mL. Through process optimization, the extraction efficiency and purity of the microalgae PDRN are improved, and the extracted PDRN has excellent anti-aging and anti-inflammatory effects.

Methods and apparatus for obtaining representations of proteins and small molecule drugs for synthesis; wherein pre-trained mixed modality protein and natural language fusion models are further trained by supervised fine tuning using reasoning-oriented query—chain-of-thought (CoT) response pairs. The resulting reasoning-oriented neural network is then used to obtain representations of output proteins or small molecule drugs, in response to mixed modality reasoning-oriented input queries specifying conditions on the output. In one embodiment, the neural network is an autoregressive multicapitate transformer whose decoder output heads correspond to the represented modalities. The method returns mixed modality output representations of proteins or small molecule drugs for synthesis or manufacture.

Provided is an antibacterial peptide having an amino acid sequence X1KRFKKFFX2KLKKWV-NH2, wherein X1 is selected from any one or of amino acids A, C, D, E, F, G, H, K, L, N, M, P, Q, R, S, I, V, W, Y, and T or is absent; and X2 is an amino acid having an aromatic side chain or an amino acid having an alkaline side chain. In view of defects such as poor gastrointestinal fluid stability of antibacterial peptides in the prior art, a brand-new sequence design scheme and preparation method for an antibacterial peptide are provided. By means of a complete or partial D-amino acid substitution or structural derivatization of a peptide sequence, a series of antimicrobial peptides having stronger antibacterial activity and gastrointestinal stability as compared with the prior art are obtained, such that the antibacterial peptides have a wider application range and higher development potential value.

The present application discloses a continuous dynamic and efficient devolatilization method for a polymer / volatile system based on high mass transfer interfaces, including the following steps: providing a dynamic single-screw devolatilizer, feeding a polymer solution to the devolatilizer, wherein the polymer solution includes polymer and volatile substances with small molecule weight, and the volatile substances include organic solvents, residual monomers, water or reaction by-products; conveying and compressing polymer materials by the screw downstream a devolatilization section, and extruding the polymer materials out of the dynamic single-screw devolatilizer directly; or providing a side-feeding extruder downstream of the devolatilization section and feeding plastic additives into a devolatilized polymer melt, and then melt blending the plastic additives with the devolatilized polymer melt at an end of the dynamic single-screw devolatilizer before exiting the dynamic single-screw devolatilizer.

The invention provides a micromolecular recombinant XVII type collagen as well as a preparation method and application thereof, and relates to the technical field of protein engineering. The novel recombinant human XVII type collagen is obtained by optimizing and screening a plurality of spiral region sequences such as a collagen structural domain, a C-terminal region and a middle region of the human XVII type collagen. The amino acid composition of the recombinant XVII type collagen is consistent with that of a natural collagen alpha1 chain, immunological rejection is not generated when the recombinant XVII type collagen is applied to a human body, the recombinant XVII type collagen can be widely applied to surgical medical treatment and medical beauty industries, the molecular weight of the collagen is small, efficient secretion soluble expression in eukaryotic host cells such as pichia pastoris can be achieved, and the recombinant XVII type collagen has a good application prospect. And industrial large-scale production is carried out. According to the present invention, the verification results show that the micromolecular recombinant XVII type collagen further has basement membrane anti-aging activity, wherein the basement membrane anti-aging activity specifically comprises the improvement of the expression levels of the IV type collagen, the VII type collagen and the XVII type collagen;

The invention relates to the field of medicinal chemistry, and particularly discloses a piperidine derivative as well as a pharmaceutical composition, application and a preparation method thereof. The piperidine derivative has the following general formula. The piperidine derivative can be effectively used for treating or preventing multiple sclerosis, and shows an unexpected synergistic effect in an animal model: the piperidine derivative not only can significantly improve neurological function impairment and promote recovery, but also can deeply reduce the levels of key proinflammatory cytokines IFN-gamma and IL-17 at the same time. The invention provides a novel small molecule candidate drug with central permeability, neuroprotection and comprehensive immune regulation functions for treatment of multiple sclerosis.

The invention discloses a micromolecule NSD3 degradation agent as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The invention provides a micromolecular NSD3 degradation agent, which has a structure as shown in a formula I or a formula II, has a remarkable inhibition effect on NSD3 protein expression, and has remarkable killing and growth inhibition effects on lung squamous carcinoma cells. The small molecule NSD3 degradation agent provides a new scheme for treatment of lung squamous cell carcinoma, and has a good clinical application prospect. # imgabs0 # imgabs1 #

The invention discloses camel milk polypeptide with xanthine oxidase inhibitory activity and application thereof.The camel milk polypeptide is prepared by taking fresh camel milk as a raw material, conducting low-temperature centrifugation to remove fat, conducting triple enzymolysis through papain, pepsin and trypsin to obtain enzymatic hydrolysate, enabling the enzymatic hydrolysate to pass through an ultrafiltration membrane (the molecular weight cutoff is 10 kDa) to obtain filtrate, and conducting freeze-drying to obtain the camel milk polypeptide. The compound has xanthine oxidase inhibitory activity. The invention also discloses a small molecule polypeptide with xanthine oxidase inhibitory activity. The filtered solution is screened and combined with polypeptides by adopting a xanthine oxidase affinity ultrafiltration method, the activity of the polypeptides is verified through molecular docking and in-vitro enzyme inhibition, four small-molecule polypeptides with xanthine oxidase inhibitory activity are obtained, the sequence of the small-molecule polypeptides is shown as any one of SEQ ID NO.1-4, and the small-molecule polypeptides can be used for preparing drugs with the effect of inhibiting the uric acid level.

The invention discloses application of a small molecule compound in prevention and treatment of plant RNA virus infection, and belongs to the technical field of biology. According to the invention, 2 '-amino-2'-deoxyguanosine (ADG) is used as a unique antiviral active component to be applied to prevention and treatment of plant RNA viruses for the first time, and broad-spectrum inhibition of various plant RNA viruses such as turnip mosaic virus (TuMV), tomato mosaic virus (ToMV) and tobacco mosaic virus (TMV) can be realized only by a low concentration of 250 [mu] M and a simple exogenous spraying mode; and after spraying, the normal growth of plants is not influenced, the risk of phytotoxicity is thoroughly avoided, the safety, high efficiency and broad spectrum of plant RNA virus prevention and control are remarkably improved, and important practical application significance is achieved for guaranteeing the yield and quality of crops in agricultural production and promoting agricultural green transformation.

The invention relates to a PLpro protease small-molecule inhibitor for treating or preventing coronavirus infection and application of the PLpro protease small-molecule inhibitor. Specifically, the invention relates to a compound shown as a formula (I) or an isotope labeled compound thereof, or an optical isomer, a geometric isomer, a tautomer or an isomer mixture thereof, or a pharmaceutically acceptable salt thereof, or a prodrug thereof, or a metabolite thereof, and the use thereof in the preparation of a medicament for treating or preventing coronavirus infection or diseases or symptoms caused by coronavirus.

The invention relates to the field of molecular targeted therapy, and discloses an application of an SLC16A5 (MCT6) small-molecule inhibitor MCT6-Ai7-2 in preparation of a medicine for treating acute myeloid leukemia (AML). The inhibitor takes an SLC16A5 protein structure predicted by Alphafold as a target spot, and is obtained through compound database screening, molecular docking and druggability optimization. An in-vitro experiment proves that MCT6-Ai7-2 can remarkably inhibit proliferation of AML cell lines such as U937 and MOLM-13, induce cell apoptosis and retard a cell cycle, has an inhibiting effect on a primary AML patient specimen and is relatively low in toxicity to normal cells; in-vivo experiments show that the compound is effective and has good safety in AML model mice. In addition, the MCT6-Ai7-2 and the vinca can be combined to synergistically enhance the inhibition effect on vinca drug-resistant cells, and by reducing the expression of anti-apoptotic protein MCL-1, the activation of pro-apoptotic factors BIM and tBID is promoted to play a role. The invention provides a novel targeting drug and strategy for treatment of AML (especially drug-resistant or recurrent patients).

The invention discloses an organic wastewater adsorbent as well as a preparation method and application thereof, and belongs to the technical field of sewage treatment. Comprising the following steps: carrying out nitration reaction on styrene porous microsphere resin, and then carrying out reduction reaction to obtain amino-modified porous microsphere resin; the preparation method comprises the following steps: carrying out polymerization reaction on high-nitrogen-content amino organic small molecules and aldehyde group small molecules under the action of a basic catalyst in an adsorption polymerization manner to generate a nitrogen-doped organic porous polymer, and coating the surface of amino-modified porous microsphere resin with the nitrogen-doped organic porous polymer to obtain the organic wastewater adsorbent. The porous microsphere resin adsorbent with large adsorption capacity and high organic matter removal rate is synthesized by using the carrier advantage of styrene microsphere resin and introducing a porous heteroatom polymer on the microsphere resin. When the adsorbent is used, the adsorbent is directly added into an organic wastewater solution, and the removal rate of bisphenol A, aniline and tetracycline can reach 90% or above.

The invention discloses a high-valued graded utilization method of marine shells, and belongs to the technical field of comprehensive utilization of biological resources and preparation of functional materials. The method comprises the following steps: cleaning, air-drying and superfine grinding marine shell wastes such as abalone shells, and extracting water-soluble organic components in the marine shell wastes by adopting mild water extraction, so that the obtained extract is rich in protein, polysaccharide or small molecule peptide, has good biological activity, and can be used for preparing functional materials such as biomimetic mineralization, tissue repair and the like; extracted shell powder residues are subjected to heat treatment or chemical activation treatment and then compounded with natural polymer materials such as chitosan and sodium alginate, and the composite adsorbent which is loose in structure and large in specific surface area is prepared and can be used for removing dye, heavy metal, antibiotics and other water pollutants. According to the invention, separate utilization of organic components and inorganic framework materials in the marine shells is realized, and the method has the characteristics of environmental protection, efficient resource conversion and multifunctional application, and has a good industrial popularization prospect.

The present invention provides a discontinuous metal film with a tunneling effect, a tunneling electrode chip, and a method for preparing the same. A large-area uniform discontinuous metal film is in situ grown on a glass substrate by magnetron sputtering deposition, constructing a charge tunneling structure with a random nanoarray. The discontinuous metal film comprises a substrate and a nanogap film disposed on the substrate. The nanogap film comprises a number of randomly distributed nanoislands and a number of nanogaps. A nanogap is formed between any two adjacent nanoislands, and the nanogap is <10 nm. The thickness of the nanogap film is <100 nm. The tunneling electrode chip achieves atomic-level thickness control through high-precision thin film deposition, significantly improving the uniformity of multiple batches of devices and increasing the yield by more than 50% compared to traditional methods. This breaks through the expensive micro-nano processing limitations faced by traditional tunneling devices, has the ability to sensitively respond to different small molecule media, and can present molecular information as transient conductivity information.

The present disclosure is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In certain embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor.

The invention relates to the technical field of hydraulic fracturing exploitation of deep / ultra-deep oil and gas reservoirs, and discloses a gel-coated temporary plugging agent and a preparation method and application thereof.The gel-coated temporary plugging agent comprises a proppant inner core and a degradable gel shell coating the outer surface of the proppant inner core; the degradable gel shell is formed by a gel shell gelling solution, the gel shell gelling solution comprises small-molecule comonomers and a degradable cross-linking agent, and the small-molecule comonomers comprise acrylamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide, N, N-dimethylformamide the initiator is one or more of N, N-dimethylacrylamide, acrylic acid, hydroxyethyl acrylate, benzyl acrylate, 2-propyl acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid and N-vinyl pyrrolidone; and the initiator is one or more of N, N-dimethylacrylamide, acrylic acid, hydroxyethyl acrylate, benzyl acrylate, 2-propyl acrylic acid, 2-acrylamide-2-methylpropanesulfonic acid and N-vinyl pyrrolidone. The gel-coated temporary plugging agent can be used for effectively plugging in a fracturing time period at high temperature / ultrahigh temperature, and the flow conductivity of fractured cracks can be enhanced by exposing an internal propping agent after the gel-coated temporary plugging agent is degraded.

The invention relates to a high-activity feather hydrolyzed amino acid water-soluble fertilizer and a preparation method thereof. The preparation method comprises the steps of pretreatment, complex enzyme stepped hydrolysis, nanofiltration separation, chelation and stabilization, spray drying and the like. Feather keratin is hydrolyzed step by step through a compound enzyme, small molecule peptide and amino acid are separated in combination with a nanofiltration membrane, trace elements are added for chelation, and a drying process is optimized, so that the activity and stability of the fertilizer are remarkably improved. The feather keratin can be efficiently degraded, the problem of amino acid racemization caused by a traditional strong acid / alkali method is solved, meanwhile, energy consumption is reduced, and the requirements of modern agriculture for environment-friendly and efficient fertilizer are met.

The invention relates to the technical field of agricultural fertilizers, and particularly discloses a polypeptide fish protein flushing water-soluble fertilizer and a preparation method thereof, the water-soluble fertilizer is prepared from the following raw materials: unrotten small fish or fish sewer, edible cane sugar or brown granulated sugar, a self-prepared fish protein enzymolysis agent, a self-prepared fish protein anaerobic fermentation inoculant and water; the preparation method comprises an enzymolysis stage and a fermentation stage. The compound fertilizer can be used as a nitrogen fertilizer to replace a traditional chemical nitrogen fertilizer, or is matched with a trace element fertilizer in a compound fertilizer to be used in crop planting; the water-soluble fertilizer has the beneficial effects that the water-soluble fertilizer can supplement soil protein amino acid fertilizer nutrition and increase the content of nutritional ingredients in crops, fermented polypeptide micromolecule sugar can be directly absorbed by the crops to improve the taste, ecological organic planting is realized, meanwhile, the planting cost is reduced, and the water-soluble fertilizer is suitable for fruit and vegetable planting families, farms, picking gardens, greenhouse farmers and the like, is simple and easy to operate, and is suitable for popularization and application. Raw materials are easy to collect, low in cost and obvious in effect.

Disclosed are small molecule inhibitors of αvβ6 integrin, and methods of using them to treat a number of diseases and conditions.

Methods and apparatus for determining protein and ligand sequence, structure, and docking site given a target protein sequence and structure are presented. A multicapitate transformer architecture with a number of heads including a sequence head and a structure head is introduced, wherein given a target protein sequence and structure, a candidate ligand is generated, wherein the transformer's sequence head yields the ligand sequence and the structure head yields the ligand structure and docking site. Non-capitate weights are shared between the output heads. In one embodiment, a discriminative feature localization method is used to optimize the target protein's input structure representation towards the desired ligand effect class. The methods and apparatus presented enable design and synthesis of both peptide ligands and small molecule drugs each with specified ligand effect categories.

The invention discloses a plant lactobacillus capable of metabolizing dendrobium officinale components to generate various active small molecules and enhancing collagen synthesis promotion of skin cells, and belongs to the technical field of microorganisms. The lactobacillus plantarum (Lactobacillus plantarum) CCFM1496 obtained by screening can be used for fermenting the dendrobium officinale to generate a plurality of active substances and regulating and controlling the synthesis of skin collagen factors, and LOR (Lyclin) shows that the fermentation liquor of the dendrobium officinale fermented by the lactobacillus plantarum (Lactobacillus plantarum) CCFM1496 has a huge application prospect in the preparation of products for preventing or treating skin quality.

The invention discloses a preparation method of EVOH, and relates to the technical field of EVOH. According to the method, a low-temperature (0-5 DEG C) methanol-n-hexane mixed solvent system is creatively adopted and matched with a penetration enhancer to realize synergistic extraction, so that synchronous and deep removal of polar and non-polar small molecular impurities in the EVA is finally realized, the content of impurities in the EVA is remarkably reduced, and the self-polymerization reaction of residual monomers is effectively inhibited; therefore, a key guarantee is provided for subsequent preparation of high-quality EVOH products. The film processed by the EVOH prepared by the invention has the characteristics of few crystal points and high product quality, and can be applied to the field of high-barrier packaging film materials.

Methods and apparatus for determining a representation of a protein-protein complex, given a constituent target complex of the protein-protein complex are presented; where the constituent target complex is some subset of the protein-protein complex. A recursive transformer neural network is devised, wherein for each iteration of the recursion, a representation of the output constituent protein complexed with the input constituent target complex is passed into the transformer as input for the next iteration. Some embodiments of the invention include design and manufacturing of effective synthetic biologic drugs, monoclonal antibody (mAb) drug, Antibody Drug Conjugate (ADC), peptide ligand drug, and small molecule drugs (SMDs).

The invention discloses application of an AI-driven target screening technology in anti-obesity treatment of a drug delivery system, and belongs to the field of cross fusion of biological medicine and artificial intelligence. The screening method provided by the invention comprises the following steps: selecting a signal channel target and active small molecules related to lipid metabolism; processing the signal channel target and the active small molecules through the data set to obtain an input matrix; and inputting the input matrix into a deep learning model to obtain the interaction intensity between the active small molecules and the signal path target. According to the method, an artificial intelligence technology is introduced, a deep learning model is constructed to efficiently predict the affinity between a drug and a protein target, the problems that a traditional target screening method depends on experience and is low in efficiency are solved, and target expression is subjected to experimental verification through a molecular biology method, so that the target screening efficiency is improved. A verification closed loop from calculation prediction to molecular demonstration is realized, and the biological credibility of a target screening result is proved.

The present invention relates to a biological polysaccharide hydrogel, a preparation method therefor and an application thereof. The biological polysaccharide hydrogel of the present invention is formed by means of the mixing and reaction of two solutions; the first solution is a polysaccharide derivative solution having an aldehyde on a side chain; the second solution is a polysaccharide derivative solution having a primary amine on a main chain or a side chain, or a small molecule compound solution having two or more primary amines. The preparation method of the present invention comprises preparing the first solution and the second solution, and then mixing the first solution and the second solution to form a transparent biological polysaccharide hydrogel. The biological polysaccharide hydrogel of the present invention can be applied as a vitreous substitute.