53 results about "Selective degradation" patented technology

The present disclosure relates to a novel class of bifunctional molecules that are useful in a targeted or selective degradation of a protein.

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 present disclosure relates to a novel class of bifunctional molecules that are useful in a targeted or selective degradation of a protein.

The invention discloses a CDK2 / 4 / 6 proteolysis targeting chimera as well as a preparation method, a pharmaceutical composition and application thereof, and the chemical structure of the CDK2 / 4 / 6 proteolysis targeting chimera is shown as a formula I, the CDK2 / 4 / 6 proteolysis targeting chimera or the isomer, the pharmaceutically acceptable salt, the solvate, the prodrug, the deuterated compound or the polymorphic substance thereof can induce selective degradation of CDK2, CDK4 and CDK6 through ubiquitin-proteasome, so that the phosphorylation level of RB1 is reduced, release of a transcription factor E2F is further inhibited, the process of cells from a G1 phase to an S phase is blocked, and the targeting effect of the cells is improved. Compared with an inhibitor, the compound is more efficient and low in toxicity, and can be used for treating various cancers. # imgabs0 #

The invention relates to an application of a PROTAC compound targeting M2-1 protein in preparation of an anti-RSV (Respiratory Syndrome Virus) drug, and belongs to the technical field of biological medicines. According to the invention, by constructing bifunctional micromolecules capable of simultaneously combining the M2-1 protein and CRBN E3 ubiquitin ligase, selective degradation of the M2-1 protein is realized, the limitation that the protein cannot be effectively targeted in the prior art is broken through, and a new technical approach is provided for solving the problems of single target spot, high drug resistance risk, lack of specific drugs and the like in RSV infection treatment; the method has obvious novelty and substantial progress.

The present application relates to a controllable degradation of siliconized DNA hydrogel and its preparation method and application, the hydrogel is assembled into a three-dimensional network through the DNA structure with single-stranded region in the center and linear DNA structure, and the mechanical properties and thermal stability thereof are improved through in-situ siliconization. The precisely designed single-stranded region can still be recognized and degraded by specific nucleic acid enzyme after siliconization, realizing the accurate control of selective degradation. Taking human umbilical vein endothelial cells as an example, the present application verifies the good biocompatibility of the material, and the present application can be used for cell embedding and release, and is suitable for advanced biological materials, medical, pharmaceutical and other research and application fields such as organoid culture, tissue engineering and controllable drug release.

This invention relates to binding molecules comprising a TRIM21 binding portion and a protein binding portion for the selective degradation of target proteins. The invention also relates to compositions comprising these molecules and their use in therapies. Furthermore, the invention relates to TRIM21 binding molecules and their use.

The present disclosure relates to protein degradation targeting chimera (PROTAC) molecules, further to BRM selective degradation agent compounds, and specifically provides compounds of formula (I) or pharmaceutically acceptable salts thereof, the compounds having the substituents and structural characteristics described herein. Also described are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and the use of said compound or a pharmaceutically acceptable salt thereof in medicine.

A substituted tricyclic derivative as shown in formula (II) and pharmaceutically acceptable salts, stereoisomers, pharmaceutical compositions and uses thereof. The tricyclic derivative compound has a higher selective degradation effect on BRM, and has a higher application value.

The present invention discloses a method for catalytically activating PMS to degrade organic pollutants, adding a catalyst Co x Mn 1‑x WO4 and PMS into wastewater, and degrading pollutants in water by PMS activated by Co x Mn 1‑x WO4. The quenching experiment shows that the material can effectively activate PMS to generate reactive species SO4·— and ·OH and 1 O2. The degradation experiments on several other organic dyes confirm that the catalyst can perform effective selective degradation. Four cyclic experiments verify the good stability of the solid solution material, which is expected to be used in actual wastewater treatment.

The invention relates to an STAT6 selective degradation agent compound shown in a formula (I) or a stereoisomer or pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the STAT6 selective degradation agent compound or the stereoisomer or the pharmaceutically acceptable salt thereof, and application of the STAT6 selective degradation agent compound or the stereoisomer or the pharmaceutically acceptable salt in preparation of drugs for preventing or treating STAT6-mediated diseases.

The invention belongs to the technical field of biological medicines, and particularly relates to an mTORC1 selective degradation agent containing a hydrophobic label as well as a synthesis method and application of the mTORC1 selective degradation agent. The structural formula of the degradation agent is as shown in formula I. Representative compounds have the effect of inhibiting proliferation of various tumor cells, and can provide new research and development thoughts and directions for anti-tumor drugs. .

The present invention provides novel compounds that induce selective polo-like kinase 1 (PLK1) degradation. Specifically, the present invention provides a bifunctional compound in which a PLK1 binding moiety and an E3 ubiquitin ligase-binding moiety are linked by a chemical linker. The present invention provides the compound, a method for preparing the same, and the use thereof. The compounds may be effectively utilized for preventing or treating PLK1 related diseases.

This invention belongs to the field of polymer materials, specifically a method for the complete degradation of polycarbonate plastics in polyether solvents. This invention enables the efficient and selective degradation of various types of polycarbonate plastics to obtain corresponding monomers and their derivatives under oil bath heating or microwave assistance, with or without an alkaline catalyst. This method features a simple reaction system, short reaction time, simple operation, and environmental friendliness.

The present invention 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 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. Pharmaceutical compositions based upon these bifunctional small molecules represent an additional aspect of the present invention. These compounds and / or compositions may be used to treat disease states and conditions by removing circulating proteins through degradation in the hepatocytes or macrophages of a patient or subject in need of therapy. Methods of treating disease states and / or conditions in which circulating proteins are associated with the disease state and / or condition are also described herein.

Compounds and compositions that have a Mannose 6-Phosphate Receptor Ligand bound to an Extracellular Protein Binding Ligand are provided for the selective degradation of a target extracellular protein in vivo to treat disorders mediated by the extracellular protein.

To provide methods and compositions for selective degradation of proteins.SOLUTION: In some aspects, messenger RNAs (mRNAs) are described that encode a ubiquitin pathway moiety and a binding peptide that binds a target protein, where the mRNA is encapsulated within a lipid nanoparticle. Also provided herein are mRNAs that encode at least two binding peptides, where a first binding peptide binds a ubiquitin pathway moiety and a second binding peptide binds a target protein, and where the mRNA is encapsulated within a lipid nanoparticle.SELECTED DRAWING: Figure 1A

The invention discloses an iron-based nano-enzyme targeting chimera as well as a preparation method and application thereof. According to the chimera, lipidosome is used as a carrier, a coordination active center is constructed by Plerixabor with CXCR4 high affinity and iron ions, selective adsorption of transferrin is achieved through surface chemical design, and double-target tumor targeted enrichment is achieved by means of TfR1-mediated rapid endocytosis. And meanwhile, selective degradation of CXCR4 through a lysosome way is accelerated, so that synergistic treatment of'blocking transfer signals-chemical kinetics killing 'is realized. The preparation provided by the invention has good biocompatibility and expandability. The platform has the advantages of molecular recognition, protein crown regulation and control, microenvironment response and the like, is suitable for precise treatment of various tumors with high CXCR4 expression, and can be used as a universal membrane protein degradation and chemical kinetics treatment integrated carrier to be expanded and applied.

The present invention provides a borneol and a preparation method thereof, and belongs to the technical field of daily chemical industry. The present invention adopts enzymatic hydrolysis and extraction technology, and selectively degrades the cell walls of borneol camphor branches and leaves through the catalytic action of specific enzymes under mild reaction conditions, thereby improving the extraction rate of borneol. This selective degradation not only effectively reduces the impurity content, but also significantly improves the purity of borneol. In addition, the water or buffer used in the enzymatic hydrolysis and extraction process is environmentally friendly and conforms to the concept of green chemistry. At the same time, the use of modified silica to adsorb borneol not only improves the extraction efficiency and shortens the extraction time, but also further reduces the cost of the overall extraction process through its reusable characteristics, making the entire extraction process more economical and efficient.

The invention relates to controllably degradable silicified DNA hydrogel and a preparation method and application thereof, the hydrogel is assembled into a three-dimensional network through a DNA structure with a single-chain region in the center and a linear DNA structure, and the mechanical property and thermal stability of the hydrogel are improved through in-situ silicification. The precisely designed single-chain region can still be recognized and degraded by specific nuclease after silicification, so that precisely controlled selective degradation is realized. The material takes human umbilical vein endothelial cells as an example, good biocompatibility of the material is verified, and the material can be used for cell embedding and releasing and is suitable for research and application fields of advanced biological materials, medicine, pharmacy and the like, such as organoid culture, tissue engineering, controllable drug release and the like.

Provided herein are compounds and compositions thereof for degrading engineered peptides in cells. In some embodiments, the compounds and compositions provided are useful for the treatment of cancer.

The present disclosure provides methods for identifying peptides and small molecule moieties that are capable of functionally bridging the interaction between a target protein and an E3 ubiquitin ligase to mediate the degradation of the target protein. Some moieties can degrade specific target variants, but other moieties cannot. These moieties create new substrates for the E3 ligase of interest. The described methods can produce compounds that can selectively degrade specific targets within cells, which has an impact on drug development under pathological conditions. The present disclosure also describes the use of post-translational modification enzymes such as N-methyltransferases, prolyl oligopeptidases, lactamase, hydroxylases, and dehydratases to produce modified peptides, as well as methods for their use.

The invention provides a heterocyclic compound as well as a composition and application thereof. Specifically provided is a compound represented by formula II or a pharmaceutically acceptable salt thereof. The compound has one or more of the following advantages: the structure is novel, IKZF2 can be efficiently and highly selectively degraded, the functions of T cells are inhibited and regulated, the compound is applied to treatment of tumors or diseases, and the compound has huge clinical development value.

The invention discloses a novel Aurora-A kinase (AURKA) degradation agent based on 2, 4-diphenylamine pyrimidine and a preparation method of the Aurora-A kinase degradation agent based on 2, 4-diphenylamine pyrimidine. The AURKA degrading agent of the present invention is a proteolytic targeting chimera (PROTAC), which recruits the AURKA protein into an optimized CRBN E3 ubiquitin ligase via a linker. The compounds can induce selective AURKA degradation and are useful in the treatment of cancer.

The invention discloses a PROTAC compound for degrading PAK5 as well as a preparation method and application of the PROTAC compound, and belongs to the technical field of biological medicines. The PROTAC molecule provided by the invention has obvious enzymatic activity for inhibiting PAK5 kinase and has good protein degradation activity on PAK5, so that the PROTAC molecule can be used for preparing a targeted PAK5 inhibitor or a targeted PAK5 degradation agent, and the PROTAC molecule provided by the invention also has a good selective degradation effect on PAK5 and can be used for preparing a targeted PAK5 inhibitor or a targeted PAK5 degradation agent. Particularly, the compound PL15 shows high selectivity for PAK5 protein degradation activity of more than 1000 times, so that the PROTAC molecule provided by the invention has relatively good application potential in treatment of tumors such as breast cancer and liver cancer mediated by PAK5.

A composition and method for the selective degradation of integrins, for example, used in the treatment of fibrosis, is provided. The compound of interest is a bifunctional integrin degradation molecule comprising a TG2 binding moiety linked to an integrin binding moiety.

The present disclosure relates to a novel class of bifunctional molecules that are useful in a targeted or selective degradation of a protein.

The invention discloses a targeted DNA homologous recombinant protein RAD51 degradation agent and application thereof, and relates to the technical field of drug synthesis. The degradation agent is designed through a targeted protein chemical knock-down technology and has the following structural general formula, in the formula, X1 is selected from bromine, chlorine, hydroxyl, methyl, trifluoromethyl, linear alkyl or p-methoxyphenyl; x2 is selected from hydrogen or fluorine; x3 is selected from hydrogen or fluorine; r is selected from halogen, methyl, methoxyl, trifluoromethyl, phenyl, benzyl, nitryl, nitrile group, 2 / 3-thienyl, 2 / 3-pyridyl, 2 / 3-furyl, N-pyrazolyl or pyridyl; the value of m is 0 or 1; n is 0 or 1; the connecting arm Linker is at least one of an aromatic chain containing at least one tertiary amine group, an aliphatic heterocyclic structure chain and an aromatic heterocyclic structure chain. The degradation agent provided by the invention can obviously and selectively degrade RAD51 protein in tumor cells, and a new scheme is provided for developing tumor treatment drugs.

The present disclosure relates to a novel class of bifunctional molecules useful for targeted or selective degradation of proteins.

The invention discloses a novel chemical upgrading and recycling method for polysulfone special engineering plastics, and belongs to the technical field of solid waste treatment. According to the method disclosed by the invention, high-yield metal is adopted as a photocatalyst, and various commercialized polysulfone plastic resins and (waste) polysulfone special engineering plastics can be degraded into diaryl ether high-added-value fine chemicals in a high-selectivity manner under room-temperature visible light illumination. The method disclosed by the invention has the advantages of low energy consumption, low cost, less pollution, single selectivity and the like, and has a wide application prospect in the field of high-added-value recovery treatment of the waste polysulfone special engineering plastics.